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Item 1. Legal Proceedings

2023-05-03 compared with 2022-10-27 · 365 added, 723 removed, 851 unchanged (56% of the section changed)

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Refer to Note 5 –

Commitments and Contingencies in this Quarterly Report for further details on our legal proceedings during the nine months ended September 30, 2022.

Commitments and Contingencies in this Quarterly Report for further details on our current legal proceedings.

Ri sk Factors

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We are substantially dependent upon VASCEPA ® (icosapent ethyl), its commercialization in the United States and its development, launch and commercialization in Europe and other major markets.

In the United States, VASCEPA is facing increasing competition from generic versions of the drug.

In Europe, we are in the process of obtaining relevant pricing approvals in various countries;

however, we may not be successful in obtaining such approvals in a timely manner, or at all and, even if successfully obtained, we may not be successful in commercializing VAZKEPA in Europe or elsewhere.

Factors outside of our control make it more difficult for VASCEPA to achieve a level of market acceptance by physicians, patients, healthcare payors and others in the medical community at levels sufficient to meet our expectations for commercial success.

Our cost reduction and organizational restructuring plan may not be successful in addressing current shifts within the Company's U.S.

business and developing sales internationally.

Our promotion and supply of VASCEPA is subject to regulatory scrutiny and associated risk.

We may not be able to compete effectively against our competitors’

pharmaceutical products.

VASCEPA is a prescription-only omega-3 fatty acid product.

Omega-3 fatty acids are also marketed by other companies as non-prescription dietary supplements.

As a result, in the U.S., VASCEPA is subject to non-prescription competition and consumer substitution.

The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including adequacy of product reimbursement which can vary from country to country.

In the United States, we face increasing competition from generic drug companies in the near term and our revenues and results could continue to be materially and adversely affected.

In Europe, we are seeking relevant pricing approvals in various countries;

however, we may not be successful in obtaining such approvals in a timely manner, or at all, and even if successfully obtained, we may not be successful in commercializing VAZKEPA in Europe.

The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including if we are unable to secure favorable product reimbursement levels, which can vary from country to country.

If we are unable to realize product reimbursement rates at reasonable levels, or at all, patient access to VASCEPA may be limited.

Our supply of product for the commercial market and clinical trials is dependent upon relationships with third-party manufacturers and suppliers.

Our dependence on third parties in the distribution channel from our manufacturers to patients subject us to risks that limit our profitability and could limit our ability to supply VASCEPA to large market segments.

Our commercialization of VASCEPA outside the United States is substantially dependent on third parties and other circumstances outside our control.

We are dependent on patents, proprietary rights and confidentiality to protect the commercial value and potential of VASCEPA.

Our issued patents may not prevent competitors from competing with VASCEPA, even if we are successful in enforcing our patent rights.

There can be no assurance that any of our pending patent applications relating to VASCEPA or its use will issue as patents.

Our previous cost reduction and organizational restructuring plans, and any similar efforts we may undertake in the future, may not be successful in mitigating risks and challenges associated with our U.S.

business and establishing a more significant international footprint.

The manufacture, supply and commercialization, including promotional activities, of VASCEPA is subject to regulatory scrutiny.

We may not be able to compete effectively against our competitors’

pharmaceutical products, including generic products.

In addition, we face competition from omega-3 fatty acids that are marketed by other companies as non-prescription dietary supplements, subjecting us to non-prescription competition and consumer substitution.

Our supply of product for the commercial market and clinical trials is dependent upon relationships with third-party manufacturers and suppliers, including manufacturers and suppliers who may require us to comply with burdensome minimum purchase commitments, which may be greater than our supply needs.

Our dependence on third parties in the distribution channel from our manufacturers to patients subjects us to risks that limit our profitability and could limit our ability to supply VASCEPA to large market segments.

We have limited experience commercializing VASCEPA outside the United States, and we may not be successful in building an infrastructure, including a sales force, that can navigate the regulatory and other dynamics outside of the United States.

We are currently, and may continue to be, substantially dependent on third parties for our international efforts, and

we may not be successful in negotiating or establishing relationships with business partners to support and maintain control over our international activities.

We are dependent on patents, proprietary rights and confidentiality obligations of our employees, agents, business partners and third parties to protect the commercial value and potential of VASCEPA.

Enforcing our patent rights is challenging and costly and, even if we are able to successfully enforce our patent rights, our issued patents may not prevent competitors from competing with VASCEPA.

We have pending patent applications relating to VASCEPA and its use.

There can be no assurance that any of these applications will issue patents, and even if patent protection is obtained, it may be insufficient to minimize competition or support our commercialization efforts.

The summary risk factors described above should be read together with the text of the full risk factors below and in the other information set forth in our Annual Report and this Quarterly Report on Form 10-Q, including our consolidated financial statements and the related notes, as well as in other documents that we file with the SEC.

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We are substantially dependent upon VASCEPA (icosapent ethyl), its commercialization in the United States and its development, launch and commercialization in Europe and other major markets.

In the United States, VASCEPA is facing increasing competition from generic versions of the drug.

In Europe, we are in the process of obtaining relevant pricing approvals in various countries;

however, we may not be successful in obtaining such approvals in a timely manner or at all and even if successfully obtained, we may not be successful in commercializing VAZKEPA in Europe or elsewhere.

The success of our company depends on our ability to successfully commercialize our only product, VASCEPA (icosapent ethyl) capsules, in major markets globally.

In recent years and currently, much of our financial results and revenue has been dependent on our ability to execute our development and commercial strategy for VASCEPA in the United States.

Generic versions of VASCEPA launched in the United States for the 1-gram capsule in November 2020, June 2021, January 2022 and for the 0.5-gram capsule in September 2022.

We expect that VASCEPA could face more competition from generic companies in the United States in the near term in light of the patent litigation rulings against us, applicable only in this territory.

Increasing sales of generic versions of VASCEPA could continue to have a material and adverse impact on our revenues and results of operations in the United States.

In June 2022, we implemented a cost and organizational restructuring plan, which included a further reduction to our U.S.

commercial team from approximately 300 sales representatives to approximately 75 sales representatives.

Although this has resulted in an improved expense structure, such efforts could impact employee morale and make hiring and retaining talented personnel more challenging, may not result in all of the cost-savings or other benefits we anticipate and are costly to implement.

We continue our development efforts to support commercialization of VASCEPA in major markets outside the United States.

In March 2021 we announced that the European Commission, or the EC, approved the marketing authorization application for icosapent ethyl, under the brand name VAZKEPA, hereafter along with VASCEPA, collectively referred to as VASCEPA, to reduce the risk of cardiovascular events in high-risk, statin-treated adult patients who have elevated triglycerides (≥150 mg/dL) and either established cardiovascular disease or diabetes and at least one additional cardiovascular risk factor.

This process is conducted on a country-by-country basis and is time-consuming and complex.

On March 25, 2022, Amarin received its first national reimbursement in a European country with official confirmation that the Swedish Dental and Pharmaceutical Benefits Agency, or TLV, approved VAZKEPA for national reimbursement in Sweden.

On July 13, 2022 the UK’s National Institute for Health and Care Excellence, or NICE, announced final guidance for reimbursement for VAZKEPA ® and use across the National Health Service, or NHS, in England and Wales to reduce the risk of CV events in adult statin-treated patients at high cardiovascular risk who have elevated triglycerides (≥150 mg/dL [≥

1.7 mmol/L]), LDL-C levels >1.04 mmol/L (and ≤

2.60 mmol/L) and established cardiovascular disease.

In August 2022, we announced that we discontinued business operations in Germany following the conclusion of negotiations with the National Association of Statutory Health Insurance Funds during which a viable agreement on the reimbursement price of VAZKEPA could not be reached.

Although the matter is now moving to the Arbitration Board for a final decision, and although we plan to resubmit a pricing and reimbursement dossier with new data in Germany once we have a new dossier ready, we may be unable to resume operations, including commercialization efforts, in Germany.

We are in the process of obtaining further pricing and reimbursement approvals for VAZKEPA in relevant jurisdictions in Europe.

As of September 30, 2022, in Canada reimbursement coverage is approximately 70% of publicly covered lives and 95% for private coverage.

Public reimbursement is now available in Ontario, Quebec, Saskatchewan, New Brunswick Northwest Territories and for the Non-Insured Health Benefits program for the First Nations and Inuit people.

We may not be successful in obtaining additional approvals in a timely manner with acceptable terms, or in additional countries.

Our expansion and development of VASCEPA outside the United States is generally not subject to the adverse patent ruling in the United States.

Development outside the United States is primarily based on the REDUCE-IT indication approved for VASCEPA in the United States.

That second indication, which we believe has significantly more value potential, is for use of the drug in the reduction of cardiovascular risk in select high-risk patients.

We have been developing VAZKEPA on our own in Europe for the approved cardiovascular risk reduction indication and are exploring possible strategic collaborations in smaller markets within Europe and in other major markets.

We currently have multiple partners for the development and commercialization of VASCEPA in select geographies and are assessing potential partners to

commercialize VASCEPA in other parts of the world.

For example, we have strategic collaborations for the development and commercialization of VASCEPA in Canada, the Middle East and Greater China.

However, we cannot make any guarantees as to the success of these efforts or that our beliefs about the value potential are accurate, and if commercialization plans for VASCEPA do not meet expectations in major markets such as the United States and Europe, our business and prospects could be materially and adversely affected.

The development and commercial time cycle for VASCEPA or other products that we may develop from our research and development efforts could result in delays in our ability to achieve commercial success.

For example, it took over a decade of preceding product development before we received marketing approval for VAZKEPA in March 2021 from the EC.

We currently derive substantially all of our revenue from sales of VASCEPA.

We may be substantially dependent on sales of VASCEPA for many years.

Our financial condition and the success of our company will be materially adversely affected, we may have to further restructure our current operations, and our business prospects will be limited, if we experience any negative developments relating to VASCEPA.

For example, in the first quarter of 2020, the U.S.

District Court for the District of Nevada issued a ruling in favor of two generic drug companies, Dr.

Reddy's Laboratories, Inc., or Dr.

Reddy's, and Hikma Pharmaceuticals USA Inc., or Hikma, and certain of their affiliates, that declared as invalid several patents of ours protecting the first U.S.

FDA-approved use of our drug, to reduce severely high triglyceride levels, or the MARINE indication.

We were unsuccessful in our appeals and our stock price was adversely and materially impacted by the ruling, the results of the appeals process and the introduction of generic competition.

If other proprietary rights protecting VASCEPA or its use are challenged, our stock price could further decline, particularly if such challenges, which are costly to defend, are successful.

Although we are exploring ways to broaden our development and commercial pipeline, such efforts are likely to be time consuming, costly and may utilize resources that could otherwise be focused on commercializing VASCEPA.

It took over a decade of preceding product development before we received marketing approval for VAZKEPA in March 2021 from the European Commission, or the EC.

Likewise, if we seek to diversify our development programs or product offerings through licensing or acquisitions, such transactions are also time consuming, may be dilutive to existing shareholdings, and may be initially disruptive to operations.

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In the United States, we face increasing competition from generic drug companies in the near term and our revenues and results of operations could continue to be materially and adversely affected.

On March 30, 2020, following conclusion of a trial in late January 2020, the U.S.

District Court for the District of Nevada, or the Nevada Court, issued a ruling in favor of two generic drug companies, Dr.

Reddy’s Laboratories, Inc., or Dr.

Reddy’s, and Hikma Pharmaceuticals USA Inc., or Hikma and certain of their affiliates, or, collectively, the Defendants, that declared as invalid several patents of ours protecting the first U.S.

FDA-approved use of our drug, for use to reduce severely high triglyceride levels, which is known as the MARINE indication.

We sought appeals of the Nevada Court judgment up to the United States Supreme Court, but, we were unsuccessful.

In November 2020, Hikma launched its generic version of VASCEPA on a limited scale and with a label that reflects the MARINE indication, and revised labeling based on the results of the REDUCE-IT trial.

On November 30, 2020, we filed a patent infringement lawsuit against a Hikma affiliate for making, selling, offering to sell and importing generic icosapent ethyl capsules in and into the United States in a manner that we allege has induced the infringement of patents covering the use of VASCEPA to reduce specified cardiovascular risk.

On January 25, 2021 we expanded the scope of this patent infringement lawsuit to include a health care insurance provider, Health Net, LLC.

On January 4, 2022, the district court hearing the case granted Hikma's motion to dismiss.

On October 13, 2022, the district court granted final judgement on the aspect of the litigation relating to the Company and Hikma.

The Company intends to appeal the decision of the district court now that it is permitted to do so and also intends to continue to vigorously pursue its ongoing litigation with Health Net, but cannot predict the outcome or the impact on its business.

In June 2021, Dr.

Reddy's launched its generic version of VASCEPA with labeling that is substantially similar to labeling of the Hikma generic product.

In January 2022, Apotex Inc., or Apotex, launched its generic version of VASCEPA with labeling that is substantially consistent with the labeling of the other generic products.

In September 2022, Teva Pharmaceuticals USA, Inc., or Teva, lauched its generic version of VASCEPA's 0.5-gram capsule with consistent labeling as the other generic products.

The rulings of the Nevada Court and related appeal losses detailed above could permit each of Teva and Apotex to launch a generic version of VASCEPA under certain circumstances pursuant to their respective settlement agreement with us.

For example, Teva and Apotex settlement agreements permit such companies to launch their generic version of VASCEPA under royalty-free licenses from us given that our petition for en banc Federal Circuit review was not granted, after issuance of the Federal Circuit mandate on November 12, 2020.

Each generic launch is subject to procurement of adequate product supply.

Following the patent litigation rulings against us, generic versions of VASCEPA began launching in the United States in November 2020, and several generic versions are currently available including for both the 0.5-gram and 1-gram capsules, and we expect that VASCEPA could face more competition from generic companies in the United States.

Increasing sales of generic versions of VASCEPA could continue to have a material and adverse impact on our revenues and results of operations in the United States.

Generally, once a generic version of a drug is available in the market, the generic version is typically used in many U.S.

states to fill a prescription for any use of the drug, subject, to state reimbursement laws.

Although, in our case, use of generic versions of VASCEPA, whether with primarily a MARINE indication label or REDUCE-IT indication label, could be further subject to the potential for patent infringement under certain case law and subject to certain Teva and Apotex settlement agreement terms, we currently face generic competition from Hikma's, Dr.

Reddy’s, Apotex's and Teva's (0.5-gram only) generic versions of VASCEPA in the United States, and could face increased competition from these or additional generic entrants in the near term, which could have a material and adverse impact on our revenues and our results of operations.

There can be no assurance that we will be successful in preventing use of generic versions of VASCEPA in indications for which they have not been approved by U.S.

states to fill a prescription for any use of the drug, subject to state substitution laws.

Although, we intend to vigorously defend our intellectual property rights related to VASCEPA, there can be no assurance that we will be successful in preventing use of generic versions of VASCEPA in indications for which they have not been approved by U.S.

FDA, even if such use is determined to infringe certain of our patent claims.

Although we continue to believe that VASCEPA is difficult to manufacture and that building capacity to manufacture VASCEPA would be time-consuming and expensive for generic companies, we do not have direct visibility into the supply levels of any of the generic companies and we rely on our own experience together with information from third parties, which information may not be reliable.

As such, generic companies could potentially find or develop sources of qualified VASCEPA supply that are not known to us

and that are more efficient or less expensive than our sources.

Furthermore, generic companies could potentially convince suppliers to prioritize supply to the generic companies.

Given the changing dynamic in the U.S.

market, we initiated cost and organizational restructuring plans which reduced our U.S.

commercial team from approximately 300 sales representatives to approximately 75 sales representatives by the end of 2022.

Although this streamlining has resulted in an improved expense structure, such efforts could impact employee morale and make hiring and retaining talented personnel more challenging, may not result in all of the cost-savings or other benefits we anticipate and are costly to implement.

In Europe, we are seeking relevant pricing approvals in various countries;

however, we may not be successful in obtaining such approvals in a timely manner or at all and even if successfully obtained, we may not be successful in commercializing VAZKEPA in Europe.

We continue our development efforts to support commercialization of VASCEPA in major markets outside the United States, particularly in light of the level of competition, including from generic products, in the United States.

This process is conducted on a country-by-country basis and is time consuming and complex, and, even though the EC approved the marketing authorization for VAZKEPA in March 2021, and we have received positive national pricing and reimbursement decisions in England and Wales, Sweden and Finland, there is no guarantee that we will be able to negotiate and obtain further reimbursement and pricing terms on favorable terms, or at all, in the countries where we are pursuing commercialization.

Further, successful progress or pricing terms in one country may not be indicative of our outcomes in other jurisdictions.

For example, although the UK’s National Institute for Health and Care Excellence, or NICE, announced final guidance for reimbursement for VAZKEPA® and use across the National Health Service, or NHS, in England and Wales, we decided to discontinue business operations in Germany following the conclusion of negotiations with the National Association of Statutory Health Insurance Funds during which a viable agreement on the reimbursement price of VAZKEPA could not be reached.

The Arbitration Board process concluded without an agreement in November 2022 and although we plan to resubmit a pricing and reimbursement dossier with new data in Germany, we may be unable to resume commercial operations in Germany.

We may not be successful in obtaining additional approvals in a timely manner with acceptable terms, or in additional countries, and if we are unable to do so, and continue to face increased competition in the United States, our financial position could be materially and adversely impacted.

We have been developing VAZKEPA on our own in Europe, where we have limited experience.

We are exploring possible strategic collaborations in smaller markets within Europe and in other major markets, which will increase our reliance on third parties, over whom we have limited control.

We currently have multiple partners for the development and commercialization of VASCEPA in select geographies and are assessing potential partners to commercialize VASCEPA in other parts of the world.

We have strategic collaborations for the development and commercialization of VASCEPA in Canada, the Middle East, Australia, New Zealand and Greater China.

However, we cannot make any guarantees as to the success of these efforts or that our beliefs about the value potential are accurate, or that we will be able to rely upon these third parties;

if commercialization plans for VASCEPA do not meet expectations in major markets such as the United States and Europe, our business and prospects could be materially and adversely affected.

If we are unable to realize product reimbursement rates at reasonable levels, or at all, patient access to VASCEPA may be limited.

There can be no assurance as to the market for VASCEPA outside the United States, or we may face challenges in successfully achieving market opportunities available to us.

Despite having received EC approval to commercialize VAZKEPA in Europe and approval elsewhere around the world, applicable regulatory agencies may impose restrictions on the product’s conditions for use, distribution or marketing, and in some cases may impose ongoing requirements for post-market surveillance, post-approval studies or clinical trials, any of which could limit the market opportunity, or our ability to capitalize on such opportunity, for VASCEPA.

Further, securing adequate reimbursement is critical for commercial success of any therapeutic and pricing and reimbursement levels of medications in markets outside the United States can be unpredictable and vary considerably on a country-by-country basis.

In some foreign countries, including major markets in Europe, the pricing of prescription pharmaceuticals is subject to governmental control.

In these countries, pricing negotiations with individual governmental authorities can take six to 12 months or longer after the receipt of regulatory marketing approval for a product, and is not always successful.

For example, after the conclusion of negotiations with the National Association of Statutory Health Insurance Funds, a viable agreement on the reimbursement price of VAZKEPA in Germany could not be reached.

As a result of the negotiation outcome, we discontinued our German operations as of September 1, 2022.

In November 2022, the Arbitration Board process concluded without an agreement.

Further, in certain European countries, securing product reimbursement is a requisite to commercial launch.

To obtain reimbursement or pricing approval in some countries, we may be required to conduct a pharmacoeconomic study that compares the cost effectiveness of VASCEPA to other available therapies.

Such pharmacoeconomic studies can be costly and the results uncertain.

The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted at this time.

Our business could be harmed if reimbursement of our products is unavailable, delayed or limited in scope or amount or if pricing is set at unsatisfactory levels.

If the pricing and reimbursement levels of VASCEPA are lower than we anticipate, then affordability of, and market access to, VASCEPA may be adversely affected and thus market potential in these territories would suffer.

We, or our partners, may even choose to not proceed with marketing VASCEPA in a market, even after obtaining all necessary regulatory approval, due to negative commercial dynamics.

Further, with regard to any indications for which we may gain approval in territories outside the United States, the number of actual patients with the condition included in such approved indication may be smaller than we anticipate.

In addition, we could face competition from products similar or deemed equivalent to VASCEPA in various jurisdictions through regulatory pathways that are more lenient than in the United States or in jurisdictions in which we do not have exclusivity from regulations or intellectual property.

If any of these market dynamics exist, the commercial potential in these territories for our product would suffer.

We have limited experience as a company in commercializing VASCEPA outside of the United States and may be unsuccessful in developing sales internationally.

While we have been working internally and with partners to support efforts toward approvals and commercialization outside the United States in light of the REDUCE-IT results and the EC approval of VAZKEPA, we may be unsuccessful in expanding our global footprint.

For example, we are launching VAZKEPA on our own in the most commercially significant markets in Europe.

The commercial launch of a new pharmaceutical product is a complex and resource heavy undertaking for a company to manage and be impacted by decisions by and interactions with local regulators, and we have no prior experience as a company operating a commercial-stage pharmaceutical business in Europe.

For example, a viable agreement on the reimbursement price of VAZKEPA in Germany could not be reached with German regulators and we have discontinued our Germany business operations.

We may be unsuccessful in expanding our global footprint.

We are launching VAZKEPA on our own in the most commercially significant markets in Europe.

The commercial launch of a new pharmaceutical product is a complex and resource heavy undertaking for a company to manage and may be impacted by decisions by and interactions with local regulators.

We have no prior experience as a company operating a commercial-stage pharmaceutical business in Europe.

As noted above, a viable agreement on the reimbursement price of VAZKEPA in Germany could not be reached with German regulators and we have discontinued our Germany business operations.

Given the amount of time and resources, including capital, needed to support regulatory and commercial efforts aimed at international expansion, if we are unsuccessful or delayed in generating revenues overseas, our results of operations could be materially and adversely impacted.

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the impact of the expiration of regulatory exclusivities and entry into the market of additional generic versions of VASCEPA;

our inability to attract and retain adequate numbers of effective sales and marketing personnel, particularly in light of our recent reductions in force;

our inability to attract and retain adequate numbers of effective sales and marketing personnel and senior management, particularly in light of our recent reductions in force and turnover on the management team;

our inability to adequately train our sales and marketing personnel and our inability to adequately monitor compliance with applicable regulatory and other legal requirements;

if we have overestimated the addressable market, the inability of our sales personnel, to obtain access to or persuade adequate numbers of physicians to prescribe or patients to use VASCEPA;

the inability of our sales personnel to obtain access to or persuade adequate numbers of physicians to prescribe or patients to use VASCEPA;

overestimating the addressable market for VASCEPA;

regulators may impose restrictions on VASCEPA’s conditions for use, distribution or marketing, and may impose ongoing requirements for post-market surveillance, post-approval studies or clinical trials, which may be costly or result in label or other use restrictions;

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unforeseen costs and expenses associated with operating a new independent sales and marketing organization;

the continued or resumed impact from COVID-19 on healthcare providers, patients and personnel which may vary considerably from jurisdiction to jurisdiction, as well as on local restrictions and practices, including the complexities of having to understand and navigate multiple and evolving sets of protocols and the accessibility and rates of vaccinations in various geographies.

any continued or resumed impact from COVID-19 on healthcare providers, patients and personnel.

If we experience one or more of the setbacks described above, we may not be able to pursue international regulatory and commercial efforts in a cost effective manner, or at all, which could cause our stock price to decline.

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Drugs remain heavily scrutinized for cost containment.

As a result, payors are becoming more restrictive regarding the use of biopharmaceutical products and scrutinizing the prices of these products while requiring a higher level of clinical evidence to support the benefits such products bring to patients and the broader healthcare system.

the broader healthcare system.

These pressures are intensified where our products are subject to competition, including from biosimilars.

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Given the diverse interests in play among payors, biopharmaceutical manufacturers, policy makers, healthcare providers and independent organizations, if and whether the parties involved can achieve alignment on the matters discussed above remains unclear and the outcome of any such alignment is difficult to predict.

We are committed to working with the entire healthcare community to ensure continued innovation and to facilitate patient access to needed medicines;

however, if reimbursement of VASCEPA is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our ability to successfully commercialize VASCEPA outside of the United States may be harmed, which could have a material and negative impact on our overall business.

Government and commercial payor actions outside the United States have affected and will continue to affect access to and sales of our products

Outside the United States, we expect countries will continue to take actions to reduce their drug expenditures.

If reimbursement of VASCEPA is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our ability to successfully commercialize VASCEPA outside of the United States may be harmed, which could have a material and negative impact on our overall business.

Government and commercial payor actions outside of the United States have affected and will continue to affect access to and sales of our products.

Outside of the United States, we expect countries will continue to take actions to reduce their drug expenditures.

International reference pricing, or IRP, has been widely used by many countries outside the United States to control costs based on an external benchmark of a product’s price in other countries.

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Some countries decide on reimbursement between potentially competing products through national or regional tenders that often result in one product receiving most or all of the sales in that country or region.

Thus, there can be no certainty that we will negotiate satisfactory reimbursement or pricing rates in markets outside the United States in a timely manner, or at all, or even if we are successful in obtaining satisfactory coverage and reimbursement, we may be unsuccessful in sustaining such coverage and reimbursement, or could face challenges as to the timeliness or certainty of payment by payors to physicians and other providers, which would have a material and adverse impact on our commercialization efforts outside of the United States.

Furthermore, despite having skilled and experienced individuals deployed in such efforts, we as an organization have limited experience in navigating the pricing and reimbursement regimes, outside of the United States, which foreign regimes are varied and complex, which might hinder our effectiveness in establishing satisfactory pricing, coverage and reimbursement levels in a timely manner or at all.

Factors outside of our control may make it more difficult for VASCEPA to achieve market acceptance by physicians, patients, healthcare payors and others in the medical community at levels sufficient to meet our expectations for commercial success.

Thus, there can be no certainty that we will negotiate satisfactory reimbursement or pricing rates in markets outside of the United States in a timely manner, or at all, or even if we are successful in obtaining satisfactory coverage and reimbursement, we may be unsuccessful in sustaining such coverage and reimbursement, or could face challenges as to the timeliness or certainty of payment by payors to physicians and other providers, which would have a material and adverse impact on our commercialization efforts outside of the United States.

We as an organization have limited experience in navigating the pricing and reimbursement regimes outside of the United States.

The foreign regimes are varied and complex, and this might hinder our effectiveness in establishing satisfactory pricing, coverage and reimbursement levels in a timely manner or at all.

In January 2013, we launched VASCEPA based on the U.S.

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Guidelines for the management of very high triglyceride levels suggest that the primary goal of reducing triglyceride levels in this patient population is reduction in the risk of acute pancreatitis.

A secondary goal for this patient population is to reduce cardiovascular risk.

A secondary goal for this patient population is to reduce CV risk.

The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined and our U.S.

FDA-approved labeling and promotional efforts state this fact.

In September 2018, we announced topline results from the REDUCE-IT ® , or Reduction of Cardiovascular Events with EPA—Intervention Trial cardiovascular outcomes study of VASCEPA.

In November 2018, we announced the primary results of our REDUCE-IT cardiovascular outcomes study confirming 25% relative risk reduction for the topline primary endpoint result with multiple robust demonstrations of efficacy, including 20% reduction in cardiovascular death.

REDUCE-IT was a multinational, prospective, randomized, double-blind, placebo-controlled study, enrollment for which started in November 2011.

REDUCE-IT investigated the effects of VASCEPA on CV risk in statin-treated adults with well-controlled LDL-C 41-100 mg/dL (median baseline LDL-C:

75 mg/dL) and other CV risk factors, including persistent elevated TG 150-499 mg/dL (median baseline TG:

REDUCE-IT topline results showed the trial met its primary endpoint demonstrating an approximately 25% relative risk reduction, to a high degree of statistical significance (p<0.001), in MACE in the intent-to-treat patient population with use of VASCEPA 4 grams per day as compared to placebo.

MACE events were defined as a composite of cardiovascular death, nonfatal myocardial infarction

(MI), nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.

This result was supported by robust demonstrations of efficacy across multiple secondary endpoints.

VASCEPA was well tolerated in REDUCE-IT with a safety profile generally consistent with clinical experience associated with omega-3 fatty acids and current U.S.

FDA-approved labeling.

In December 2019, the U.S.

FDA approved another indication and label expansion for VASCEPA as an adjunct to statin therapy to reduce the risk of MACE events in adult patients with elevated TG levels (≥150 mg/dL) and established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular disease.

FDA approval for this indication and expanded label for VASCEPA, we may not meet expectations for market acceptance by physicians, patients, healthcare payors and others in the medical community for this approved use, especially in light of our unsuccessful appeals efforts.

If VASCEPA does not achieve an adequate level of acceptance, we may not generate product revenues sufficient to become profitable on an ongoing basis.

If VASCEPA does not achieve an adequate level of acceptance, we may not generate product revenues sufficient to become profitable, or, even if we do achieve profitability, we may not be able to generate consistent profitability.

The degree of market acceptance of VASCEPA for its approved indications and uses or otherwise will depend on a number of factors, including:

the impact of and outcome of pending patent litigation;

the impact of and outcome of adjudicated, settled and pending patent litigation;

the commercialization and pricing of any current or potential generic versions of VASCEPA;

the perceived efficacy and safety of VASCEPA by prescribing healthcare professionals and patients, as compared to no treatment and as compared to alternative treatments in various at-risk patient populations;

peer review of different elements of REDUCE-IT results over time;

continued review and analysis of the results of REDUCE-IT by regulatory authorities internationally;

the prevalence and severity of any side effects and warnings in VASCEPA's approved labeling internationally;

peer review of different elements of data supporting our REDUCE-IT indication over time;

continued review and analysis of the results of our clinical data supporting our REDUCE-IT indication by regulatory authorities internationally;

our ability to offer VASCEPA for sale at competitive prices;

convenience and ease of administration compared to alternative treatments;

the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

the willingness of the target patient population to try our therapies and of physicians to prescribe these therapies;

the scope, effectiveness and strength of product education, marketing and distribution support, including our sales and marketing teams;

publicity concerning VASCEPA or competing products;

our ability to continually promote VASCEPA in the United States consistent with and outside of U.S.

our ability to continually promote VASCEPA in the United States consistent with U.S.

FDA-approved labeling and the related perception thereof;

sufficient third-party coverage or reimbursement for VASCEPA and its prescribed uses, on-label and off-label;

natural disasters, including pandemics such as COVID-19 and political unrest which could inhibit our ability to promote VASCEPA regionally and which could negatively affect product demand by creating obstacles for patients to seek treatment and fill prescriptions;

natural disasters, including pandemics such as the COVID-19 pandemic, international conflicts and political unrest, all of which could inhibit our ability to promote VASCEPA regionally and which could negatively affect product demand by creating obstacles for patients to seek treatment and fill prescriptions;

new policies or laws affecting VASCEPA sales, such as state and federal efforts to affect drug pricing and provide or remove healthcare coverage that includes reimbursement for prescription drugs;

the actual and perceived efficacy of the product and the prevalence and severity of any side effects and warnings in VASCEPA’s approved labeling internationally.

For example, two major factors that affect market use of prescription drugs are their perceived cost-effectiveness and the breadth of their use among different patient populations, both on label and off-label.

In October 2019, the Institute for Clinical and Economic Review, or ICER, released its final evidence report regarding clinical effectiveness and economic impacts on VASCEPA.

The conclusion from the report is that VASCEPA easily met even the most stringent “commonly cited thresholds for cost-effectiveness and therefore represent(s) a high long-term value for money,”

based on the organization’s value assessment framework.

As part of the public meeting held by ICER analyzing REDUCE-IT data, the ICER review committee discussed whether, based on REDUCE-IT, VASCEPA should be considered for use in patients as an add-on to statin therapy generally, and not just in patients with persistent elevated triglyceride levels after statin therapy, which ICER defined as triglyceride levels of at least 135 mg/dL.

Use as an add-on to statin therapy generally represents a larger patient population than studied in REDUCE-IT and larger than covered by U.S.

FDA-approved labeling.

By contrast, U.S.

FDA-approved labeling for VASCEPA reflects limitations such as use in patients with persistent elevated triglyceride levels defined as triglyceride levels of at least 150 mg/dL after statin therapy and specific criteria designed to ensure the patient populations approved for use had sufficiently high degrees of CV risk.

While the clinical judgment of prescribing physicians is the most important factor that determines the breadth of a drug’s use in the United States and often results in prescriptions in patient populations that go beyond U.S.

FDA labeling, U.S.

FDA-approved labeling that is more closely tied to the patient population studied in a clinical trial could limit use generally and could make reimbursement more difficult.

*Despite some recent remediation of the negative impacts on our business from the COVID-19 pandemic, the evolving and continued scale, scope and duration of business interruptions caused by the ongoing COVID-19 pandemic and related recovery efforts remain uncertain.

Despite recent improvements, the global spread of COVID-19 has created significant volatility, uncertainty and disruption in healthcare, social, supply and economic infrastructures.

The extent to which the coronavirus pandemic will continue to impact our business, operations and financial results will depend on numerous evolving factors that we may not be able to accurately predict or plan around, including:

the duration, volatility and scope of the pandemic, including resurgences, and the efficacy of recovery efforts;

governmental, business and individuals’

actions that have been and continue to be taken in response to the pandemic;

the impact of the pandemic on economic and political activity and actions taken in response;

the effect on patients, healthcare providers and business partners, including patients’

ability to access supplies of VASCEPA and the willingness of patients to visit doctors for non-urgent medical examination or to visit labs for blood tests to assess biomarkers such as lipid levels;

our ability to commercialize VASCEPA, including if travel restrictions, social distancing and other containment measures are resumed or intensified;

the enrollment or monitoring of patients in clinical trials, particularly at clinical trial sites located in highly impacted jurisdictions and jurisdictions where vaccination rates are low;

the ability to access, secure and otherwise obtain and deliver sufficient and timely commercial or clinical supplies of VASCEPA at reasonable prices and sufficient to meet demand if the production capabilities of suppliers is disrupted;

disruptions in regulatory oversight and actions if regulators and industry professionals continue to expend significant and unexpected resources addressing COVID-19;

the availability of coverage and reimbursement from government and health administration authorities, private health insurers and other third-party payors if the system continues to be overly strained;

the ability of regulators to complete inspections and reviews of operations and applications, respectively, in a timely manner;

any further, prolonged or reinstated closures of our and our partners’

offices, operations and facilities impeding our ability to work together as a company and with our business and healthcare partners.

Even as the impacts of the pandemic appear to subside, additional variants may emerge and as vaccine usage and protocols evolve, face-to-face interactions may continue to be challenging for us to predict.

The circumstances surrounding COVID-19 vary geographically and vary over time, with continued risk of potential resurgences in COVID-19 cases, and the possibility of reinstitution of protocols, in various geographies as the efficacy of the vaccine on various strains remains uncertain.

While we have supplemented our face-to-face interactions with virtual outreach, these efforts may not be as impactful as traditional, in-person interactions.

Specifically, access to healthcare professionals through the internet or other channels, may not be as productive as in-person interactions.

Although we have a geographically diversified supply chain for VASCEPA and believe we have sufficient inventory on hand at pharmacies throughout the United States and other markets where it is approved for sale, and at various stages of manufacturing with

our suppliers, the global spread of the pandemic and containment measures has been unprecedented and could have a negative impact on the availability of VASCEPA at various points in our supply chain, including limiting the ability of new suppliers to be inspected, which would have a material and adverse effect on our business.

The ongoing demand for vaccines, including boosters, and potential for manufacturing facilities and materials to be commandeered under the Defense Production Act of 1950, or equivalent foreign legislation, may make it more difficult to obtain materials or manufacturing slots for the products needed for our commercial product, which could lead to issues with our commercial supply.

The disruptions associated with the coronavirus pandemic could also delay the timing of a determination on our ability to seek legal remedies as travel, operational resources and personnel are disrupted or slow to resume pre-pandemic levels, with respect to our efforts and capabilities, as well as those of our advisors and the courts.

The disruptions associated with the coronavirus pandemic could delay the potential timing of subsequent steps for the launch of commercialization of VAZKEPA in Europe.

Additionally, COVID-19 has already and could continue to limit our ability to have access with healthcare professionals to help educate them regarding VAZKEPA so that they are more likely to prescribe it to their at-risk patients.

And, similar to our experience in the United States, the effects of COVID-19 and related preventative measures may reduce the frequency at which at-risk patients seek non-urgent preventative medical care.

As with any cardiovascular outcomes trial, over time further data assessment related to REDUCE-IT by international regulatory authorities or otherwise could yield additional useful information to inform greater understanding of study outcome.

If the additional data or related interpretations do not meet expectations, the perception of REDUCE-IT results and VASCEPA revenue potential may suffer and our stock price may decline.

In December 2019, the U.S.

Even though U.S.

FDA has approved VASCEPA for this expanded label and indication based on the REDUCE-IT results, additional data assessment by international regulatory authorities or otherwise could yield additional useful information to inform greater understanding of study outcome.

Any one or more of the above factors could have a negative impact on our ability to successfully commercialize VASCEPA, which would in turn have a negative impact on our financial condition.

Additional data or related interpretations that are generated or arise over time related to REDUCE-IT might not meet expectations, and the perception of REDUCE-IT results and VASCEPA revenue potential may suffer and our stock price may decline.

While the U.S.

FDA approved the expanded label for VASCEPA for the REDUCE-IT indication in 2019, additional data assessment by international regulatory authorities or otherwise could yield additional information to inform greater understanding of study outcome, which information could impact the perception of VASCEPA.

Such data or interpretations may not be favorable for us.

Generally, trial data assessment sufficient to convey a complete picture of trial outcome can take years to complete and publish.

When new data are assessed and released or presented it could exceed, match or may not meet investor expectations.

In addition, the same set of data can sometimes be interpreted to reach different conclusions, as when Health Canada approved an indication based on REDUCE-IT data that was different in certain respects than that approved by U.S.

In addition, the same set of data can sometimes be interpreted to reach different conclusions, as when Health Canada approved an indication based on our REDUCE-IT trial data that was different in certain respects than that approved by U.S.

FDA and by the EC in Europe.

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In these instances our revenue and business could suffer and our stock price could significantly decline.

Ongoing clinical trials or new clinical data involving VASCEPA and similar moderate-to-high doses of eicosapentaenoic acid or icosapent ethyl could influence public perception of VASCEPA’s clinical profile and the commercial and regulatory prospects of VASCEPA.

Ongoing trials of moderate-to-high doses of VASCEPA and icosapent ethyl, or a similar eicosapentaenoic acid product could provide further information on the effects of VASCEPA and its commercial and regulatory prospects.

Ongoing clinical trials or new clinical data involving VASCEPA and similar moderate-to-high doses of eicosapentaenoic acid or icosapent ethyl could adversely impact public perception of VASCEPA’s clinical profile and the commercial and regulatory prospects of VASCEPA.

Ongoing trials of moderate-to-high doses of VASCEPA and icosapent ethyl, or a similar eicosapentaenoic acid product, could render new or adverse information on the effects of VASCEPA and its commercial and regulatory prospects.

For example, the Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and EPA (RESPECT-EPA;

UMIN Clinical Trials Registry number, UMIN000012069) is a study examining Japanese patients with chronic coronary artery disease receiving LDL-C lowering treatment by statin therapy.

Patients will be randomized to either a control group (standard treatment) or EPA group (standard treatment plus 1.8 grams per day of eicosapentaenoic acid), to examine the effects of a different formulation of icosapent ethyl than VASCEPA on the incidence of cardiovascular events.

The relationship between the ratio of EPA to arachidonic acid and incidence of events will also be examined.

Results from this study are expected to be presented during the 2022 American Heart Association Scientific Sessions in November 2022.

In November 2020, we announced statistically significant topline results from a Phase 3 clinical trial of VASCEPA, conducted by our partner in China, Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, which investigated VASCEPA as a treatment for patients with very high triglycerides (≥500 mg/dL).

Even though such results are similar to the results of the MARINE study, additional clinical development efforts may be necessary in this market to demonstrate the effectiveness of VASCEPA in reducing major adverse cardiovascular events in Chinese patients with persistent cardiovascular risk.

We have also funded investigational studies on the use of VASCEPA in the setting of COVID-19 infection.

On December 12, 2020, we announced at the National Lipid Association Scientific Sessions 2020 positive clinical results from the CardioLink-9 Trial, the first results of a study of VASCEPA in COVID-19 infected outpatients.

Results from the investigator sponsored study in Argentina called PREPARE-IT-1 were presented by the lead trial investigator at the European Society of Cardiology on August 29, 2021 and the results did not meet the primary and/or other endpoints studied.

Results from the investigator sponsored study in Argentina called PREPARE-IT-2 were presented by the lead trial investigator at the American Heart Association Scientific Sessions in November 2021 and the results did not meet the primary and/or other endpoints studied.

Results from the other investigational study, called MITIGATE, are expected during the first half of 2023.

If the outcomes of one or more of these studies do not meet expectations, the perception of existing clinical results of VASCEPA, such as MARINE or REDUCE-IT, or the perceived clinical profile and commercial value of VASCEPA and its regulatory status may suffer.

Results from this study were presented during the 2022 American Heart Association Scientific Sessions in November 2022 and were consistent with the evidence from the REDUCE-IT study.

Even though such results from these trials were positive, additional clinical development efforts may be necessary in these markets to demonstrate the effectiveness of VASCEPA, which may be costly to pursue, or may not produce the desired or expected results.

If the outcomes of any study involving VASCEPA and icosapent ethyl is unfavorable, the perception of existing clinical results of VASCEPA, such as MARINE or REDUCE-IT, or the perceived clinical profile and commercial value of VASCEPA and its regulatory status, or perceptions about the potential for VASCEPA, including as a treatment for broader indications, may suffer.

If this occurs our revenue and business could suffer and our stock price could significantly decline.

*Our cost reduction and organizational restructuring plan may not be successful in addressing the current shift in the United States business and developing sales internationally.

If we are not successful in our efforts to continue to market and sell VASCEPA in the United States, including from the implementation of our cost reduction and organizational restructuring plan announced in June 2022, reduced sales force, our anticipated revenues or our expenses could be materially and negatively affected, and we may not maintain profitability in the United States or obtain profitability internationally, may need to cut back on research and development activities or implement other cost-containment measures, or we may need to raise additional funding that could result in substantial dilution or impose considerable restrictions on our business.

Given the dynamics related to COVID-19, we cannot predict our ability to effectively sustain business efforts, or how those efforts will be impacted in the long term.

While we have supplemented traditional face-to-face interactions with virtual outreach, these efforts may not be as successful as in-person interactions.

Specifically, access to healthcare professionals through digital or other channels, may not be as productive as in-person interactions in promoting use of VASCEPA.

We continue to adjust our promotional initiatives, including pursuing increased face-to-face interactions with health care professionals based on COVID-19 protocols that are in place.

business and establishing a more significant international footprint.

If we are not successful in our efforts to continue to market and sell VASCEPA in the United States, including following the implementation of our cost reduction and organizational restructuring plan, our anticipated revenues or our expenses could be materially adversely affected, and we may not maintain profitability in the United States or obtain profitability internationally.

Further, we may need to cut back on research and development activities or we may need to implement other cost-containment measures, or we may need to raise additional funding that could result in substantial dilution or impose considerable restrictions on our business.

Our promotional initiatives have had to adjust over the last several years, given the impact of COVID-19 and international instability, which efforts have been costly and require considerable resources.

Shifts from traditional face-to-face interactions to mostly virtual outreach, specifically, access to healthcare professionals through digital or other channels, were not as productive as in-person interactions in promoting use of VASCEPA and we have been pursuing increased face-to-face interactions with targeted health care professionals as protocols have eased and travel has resumed to more stable levels.

Such efforts are costly and there can be no assurance that they will result in an increase in VASCEPA prescriptions and sales in the near future, or at all.

Our promotion and supply of VASCEPA is subject to regulatory scrutiny and associated risk.

The manufacture, supply and commercialization, including promotional activities, of VASCEPA is subject to regulatory scrutiny.

The Federal Food, Drug, and Cosmetic Act, or FDCA, has been interpreted by the U.S.

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Companies that market drugs for off-label uses or indications have been subject to related costly litigation, criminal penalties and civil liability under the FDCA and the FCA.

However, case law over the last several years has called into question the extent to which government in the United States, including the U.S.

However, case law over the last several years has called into question the extent to which the U.S.

government, including the U.S.

FDA, can, and is willing to seek to, prevent truthful and non-misleading speech related to off-label uses of U.S.

FDA-approved products such as VASCEPA.

In May 2015, we and a group of independent physicians filed a lawsuit against the U.S.

FDA seeking a federal court declaration that would permit us and our agents to promote to healthcare professionals the use of VASCEPA in the ANCHOR population and promote on the potential of VASCEPA to reduce the risk of cardiovascular disease so long as the promotion is truthful and

non-misleading.

This use of VASCEPA at issue reflected recognized medical practice at the time but was not approved by the U.S.

FDA and was thus not covered by then U.S.

FDA-approved labeling for the drug.

Promotion of an off-label use has generally been considered by the U.S.

FDA to be illegal under the FDCA.

The lawsuit, captioned Amarin Pharma, Inc., et al.

Food & Drug Administration, et al.

3d 196 (S.D.N.Y.

2015), was filed in the United States District Court for the Southern District of New York.

In the lawsuit, we contended principally that U.S.

FDA regulations limiting off-label promotion of truthful and non-misleading information are unconstitutional under the freedom of speech clause of the First Amendment to the U.S.

Constitution as applied in the case of our proposed promotion of VASCEPA.

The physicians in the suit regularly treated patients at risk of cardiovascular disease and, as the complaint contended, have First Amendment rights to receive truthful and non-misleading information from Amarin.

The suit was based on the principle that better informed physicians make better treatment decisions for their patients.

FDA opposed this lawsuit but did not dispute the veracity of the subject ANCHOR clinical trial data (the safety data from which was already and currently is in U.S.

FDA-approved labeling of VASCEPA) or the peer-reviewed research related to VASCEPA and the potential for cardiovascular risk reduction.

In August 2015, we were granted preliminary relief in this lawsuit through the court’s declaratory judgment that confirmed we may engage in truthful and non-misleading speech promoting the off-label use of VASCEPA to healthcare professionals, i.e., to treat patients with persistently high triglycerides, and that such speech may not form the basis of a misbranding action under the FDCA.

In August 2015, we began to communicate promotional information beyond the MARINE indication to healthcare professionals in the United States as permitted by this court declaration.

FDA did not appeal the court’s ruling.

In March 2016, we settled this litigation under terms by which the U.S.

As a result of a lawsuit that we and a group of independent physicians filed against the U.S.

FDA in 2015, we were granted preliminary relief through the court’s declaratory judgment that confirmed we may engage in truthful and non-misleading speech promoting the off-label use of VASCEPA to healthcare professionals, i.e., to treat patients with persistently high triglycerides, and that such speech may not form the basis of a misbranding action under the FDCA.

FDA did not appeal the court’s ruling and ultimately settled this litigation under terms by which the U.S.

FDA and the U.S.

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FDA-approved labeling for VASCEPA did not change as a result of this litigation and settlement, and neither government nor other third-party coverage or reimbursement to pay for the off-label use of VASCEPA promoted under the court declaration was required.

In addition to claims classically considered to be on-label based on our expanded label for VASCEPA based on the REDUCE-IT results, we proactively communicate information related to VASCEPA in a manner that we believe is truthful and non-misleading and thus protected under the freedom of speech clause of the First Amendment to the United States Constitution.

Promotional activities in the biotechnology and pharmaceutical industries generally are subject to considerable regulatory scrutiny and, even though we have the benefit of a final settlement in this litigation, our efforts may be subject to enhanced scrutiny to ensure that our promotion remains within the scope covered by the settlement.

For example, under the settlement, we remain responsible for ensuring our speech is truthful and non-misleading, which is subject to a considerable amount of judgment.

Promotional activities in the biotechnology and pharmaceutical industries generally are subject to considerable regulatory scrutiny and, may be subject to enhanced scrutiny to ensure that our promotion remains within the scope covered by the settlement.

Under the settlement, we remain responsible for ensuring our speech is truthful and non-misleading, which is subject to a considerable amount of judgment.

FDA, the U.S.

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The inquiries require us to produce documents and answer written questions, or interrogatories, relevant to specified time periods.

We are cooperating with the government.

We cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

Although we are cooperating with the government, we cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

Such investigations can be lengthy, costly and could materially affect and disrupt our business.

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We may not be able to compete effectively against our competitors’

pharmaceutical products.

pharmaceutical product, including generic products.

The biotechnology and pharmaceutical industries are highly competitive.

There are many pharmaceutical companies, biotechnology companies, public and private universities and research organizations actively engaged in the research and development of products that may be similar to our product.

It is probable that the number of companies seeking to develop products and therapies similar to VASCEPA will increase.

We expect that the number of companies seeking to develop products and therapies similar to VASCEPA will increase.

Many of these and other existing or potential competitors may have substantially greater financial, technical and human resources than we do and may be better equipped to develop, manufacture and market products.

These companies may develop and introduce products and processes competitive with, more efficient than or superior to ours.

In addition, other technologies or products may be developed that have an entirely different approach or means of accomplishing the intended purposes of our products, which might render our technology and products noncompetitive or obsolete.

other technologies or products may be developed that have an entirely different approach or means of accomplishing the intended purposes of our products, which might render our technology and products noncompetitive or obsolete.

Our competitors include large, well-established pharmaceutical and generic companies, specialty and generic pharmaceutical sales and marketing companies, and specialized cardiovascular treatment companies.

With generic versions of VASCEPA launched in the U.S.

by Hikma in November 2020, Dr.

Reddy's in June 2021, Apotex in January 2022 and Teva for the 0.5-gram capsule only in September 2022, and with the potential for further generic versions being launched, it may not be viable for us to continue to invest in market education to grow the market and our ability to maintain current promotional efforts and attract favorable commercial terms in several aspects of our business will likely be adversely affected as we face increased generic competition, or if we launch our own generic version of VASCEPA.

Woodward Pharma Services LLC currently sells Lovaza ® , which it acquired from GlaxoSmithKline plc in the third quarter of 2021.

Lovaza ® a prescription-only omega-3 fatty acid indicated for patients with severe hypertriglyceridemia, was approved by the U.S.

FDA in 2004 and has been on the market in the United States since 2005.

Multiple generic versions of Lovaza are available in the United States.

Other large companies with competitive products include AbbVie, Inc., which currently sells Tricor ® and Trilipix ® for the treatment of severe hypertriglyceridemia and Niaspan ® , which is primarily used to raise high-density lipoprotein cholesterol, or HDL-C, but is also used to lower triglycerides.

Multiple generic versions of Tricor, Trilipix and Niaspan are also available in the United States.

We compete with these drugs, and in particular, multiple low-cost generic versions of these drugs, in our U.S.

by companies such as Hikma, Dr.

Reddy's, Apotex and Teva, all of which have greater resources than us, and with the potential for further generic versions being launched, it may not be viable for us to continue to invest in market education to grow the market and our ability to maintain current promotional efforts and attract favorable commercial terms in several aspects of our business will likely be adversely affected as we face increased generic competition, or if we launch our own generic version of VASCEPA.

We also face considerable competition in the United States from branded products and generic versions of competing branded products and formulations, including Lovaza ® , Tricor, ® Trilipix ® and Niaspan ® , all of which have multiple generic competing versions.

We compete with these drugs in our U.S.

FDA-approved indicated uses, even though such products do not have U.S.

FDA approval to reduce CV risk on top of statin therapy.

In addition, in April 2014, Omtryg (omega-3-acid ethyl esters A) capsules, a free fatty acid form of omega-3 (comprised of 50% EPA and 40% DHA), developed by Trygg Pharma AS, received U.S.

FDA approval for severe hypertriglyceridemia.

Omtryg has not been commercially launched, but could launch at any time.

AstraZeneca conducted a long-term outcomes study to assess Statin Residual Risk Reduction With EpaNova in HiGh Cardiovascular Risk PatienTs With Hypertriglyceridemia, or STRENGTH.

The study was a randomized, double-blind, placebo-controlled (corn oil), parallel group design that is believed to have enrolled approximately 13,000 patients with hypertriglyceridemia and low HDL and high risk for cardiovascular disease randomized 1:1 to either corn oil plus statin or Epanova plus statin, once daily.

On January 13, 2020 following the recommendation of an independent Data Monitoring Committee, AstraZeneca decided to close the STRENGTH trial due to its low likelihood of demonstrating benefit to patients with mixed dyslipidemia who are at increased risk of cardiovascular disease.

Full data from the STRENGTH trial was presented at the AHA's Scientific Sessions in November 2020, confirming that Epanova failed to meet the primary endpoint of CV risk reduction, and published in Journal of the American Medical Association (JAMA) in December 2020.

In addition, in March 2017, Kowa Research Institute (a subsidiary of the Japanese company Kowa Co., Ltd) initiated a Phase 3 cardiovascular outcomes trial titled PROMINENT examining the effect of pemafibrate (experimental name K-877) in reducing cardiovascular events in Type II diabetic patients with hypertriglyceridemia.

In April 2022, Kowa Research Institute announced the decision to not continue the PROMINENT study as the primary endpoint was unlikely to be met.

Results of the PROMINENT trial are scheduled to be presented at the 2022 American Heart Association Scientific Session in November 2022.

During 2018, two outcomes studies were completed of omega-3 mixtures which both failed to achieve their primary endpoints of cardiovascular risk reduction and two meta-analyses were published showing that omega-3 mixtures of are not effective in lowering cardiovascular risk.

Results and analyses of these failed outcomes studies, as described below, while not done with VASCEPA, may negatively affect sales of VASCEPA if omega-3 mixtures are broadly viewed as ineffective.

For example, results of one of these two studies, the VITamin D and OmegA-3 TriaL, or VITAL, as announced immediately before the presentation of REDUCE-IT results at the 2018 Scientific Sessions of the AHA on November 10, 2018, failed to achieve its primary endpoint of lowering cardiovascular events.

VITAL was an NIH funded randomized double-blind, placebo-controlled, 2x2 factorial trial of 2000 IU per day of vitamin D3 and 1 gram per day of omega-3 fatty acid mixture supplementation (Lovaza) for the primary prevention of cancer and cardiovascular disease in a nationwide USA cohort of 25,874 adults not selected for elevated cardiovascular or cancer risk.

Likewise, in 2018, results from the other outcome study, A Study of Cardiovascular Events iN Diabetes (ASCEND) trial were released and showed negligible results for omega-3 fatty acid mixtures 1 gram daily.

ASCEND was a British Heart Foundation funded 2x2 factorial design, randomized study to assess whether aspirin 100 mg daily versus placebo and separately, omega-3 fatty acid mixtures 1 gram daily versus placebo, reduce the risk of cardiovascular events in a nationwide United Kingdom, or UK, cohort of over 15,000 individuals with diabetes who do not have ASCVD.

In a meta-analysis, presented in 2018 by the Cochrane Foundation and separately as published in JAMA, additional omega-3 studies were evaluated.

Similar to the VITAL and ASCEND studies, most of the studies in these omega-3 meta-analyses were of omega-3 mixtures, including DHA, and most were studies of relatively low doses of omega-3 as is associated with dietary supplementation and/or they studied relatively low risk patient populations.

The exception was the JELIS study, conducted in Japan, of highly pure EPA which showed a positive outcome benefit but had significant limitations in its application to a wider population.

The negative results from such omega-3 mixture studies could create misleading impressions about the use of omega-3s generally, including VASCEPA, despite REDUCE-IT positive results and the highly-pure and stable EPA active ingredient in VASCEPA and its higher dose regimen.

More recently, in 2020, an additional Nordic trial known as OMEMI failed to demonstrate a reduction in cardiovascular events with an omega-3 fatty acid mixture.

OMEMI, an investigator-initiated, multi-center, randomized clinical trial, was designed to evaluate the effects of daily treatment with omega-3 fatty acids compared with placebo among elderly patients (age 70-82) with recent myocardial infarction.

Patients received 1.8 g omega-3 fatty acids (930 mg EPA and 660 mg DH) or placebo (corn oil) daily added to standard of care.

Results presented in November 2020 at the AHA’s Scientific Sessions showed no significant differences in cardiovascular events between the treatment groups for the composite primary endpoint (non-fatal MI, unscheduled revascularization, stroke, hospitalization for heart failure or all-cause mortality), nor for the individual component of this endpoint after two years.

Matinas BioPharma, Inc., or Matinas, is developing an omega-3-based therapeutic (MAT9001 also known as LYPDISO) for the treatment of severe hypertriglyceridemia and mixed dyslipidemia.

In the fourth quarter of 2014 Matinas filed an IND with the U.S.

FDA to conduct a human study in the treatment of severe hypertriglyceridemia and, in June 2015, the company announced topline results for its head-to-head comparative short duration pharmacokinetic and pharmacodynamic study of LYPDISO versus VASCEPA in patients under conditions inconsistent with the U.S.

FDA-approved label for VASCEPA and presented results based on biomarker modification without outcomes data.

In September 2017, Matinas announced that it will be seeking a partner company to develop and commercialize LYPDISO In March 2019, Matinas announced that net proceeds from a public offering of common stock would be used for development activities for LYPDISO In March 2020, Matinas announced that it completed the clinical dosing for a comparative clinical bridging bioavailability study and the in-life portion of a 90-day comparative toxicology study in the first quarter of 2020.

Both studies were conducted to support a planned 505(b)(2) registration pathway.

In March, Matinas also initiated an additional Phase 2 head-to-head pharmacokinetic and pharmacodynamic study, ENHANCE-IT, against VASCEPA in patients with elevated triglycerides (150-499 mg/dL), while the study was paused in the first quarter of 2020 due to the COVID-19 pandemic, enrollment resumed in June and was completed in August 2020.

In the first quarter of 2021, Matinas announced topline results from the ENHANCE-IT study, stating that LYPDISO, or MAT9001, did not meet statistical significance over VASCEPA on the primary endpoint of percent change from baseline to end of treatment in triglycerides in the PD population.

A key secondary endpoint in ENHANCE-IT was the measurement of eicosapentaenoic acid levels in the blood, which is regarded as a key surrogate marker in determining cardiovascular risk reduction.

In ENHANCE-IT, plasma EPA concentrations were significantly higher with LYPDISO versus VASCEPA, with a 46% relative percentage increase in the change from baseline EPA level versus VASCEPA.

ENHANCE-IT study results were published in March 2022 in the Journal of the American Heart Association (JAHA).

Matinas has announced that the results from ENHANCE-IT suggest potential for LYPDISO as a drug for cardiovascular risk reduction and announced that it is pursuing external partnerships to further develop LYPDISO for cardiovascular outcomes indication.

As a result, Matinas no longer plans to pursue an indication for the treatment of severe HTG, instead focusing on the broader cardiovascular risk reduction indication.

In June 2018, NeuroBo Pharmaceuticals, Inc.

(previously named Gemphire Therapeutics) announced positive topline results from a Phase 2b trial, or INDIGO-1, of its drug candidate, Gemcabene, in patients with severe hypertriglyceridemia.

Gemcabene is an oral, once-daily pill for a number of hypercholesterolemic populations and severe hypertriglyceridemia.

In August 2018, the U.S.

FDA requested that Gemphire conduct an additional long-term toxicity study before commencing any further clinical testing, thereby effectively placing Gemcabene on clinical hold.

In March 2020 NeuroBo announced the completion of the requested studies, and in May 2020 the company announced that it received written communication from the U.S.

FDA that the clinical development program for Gemcabene remains on partial clinical hold for severe HTG.

In June 2019, Gemphire announced top-line clinical results from a Phase 2 trial in Familial Partial Lipodystrophy (FPL)/NASH in which Gemcabene safely met the primary endpoint in a sub-set of patients.

Phase 3 studies for homozygous familial (hypercholesterolemia, or HoFH), heterozygous familial hypercholesterolemia, or HeFH, and non-familial hypercholesterolemia in ASCVD patients are planned.

NeuroBO is currently assessing Gemcabene for additional indications, including, as an acute treatment for COVID-19.

Afimmune Ltd.

has an oral, small molecule drug candidate, epeleuton (DS-102), in development for a number of conditions of the liver, lung, and metabolic system, including hypertriglyceridemia and cardiovascular risk reduction, Phase 2 clinical trials are currently ongoing for non-alcoholic fatty liver disease, or NAFLD, chronic obstructive pulmonary disease, or COPD, and planned for hypertriglyceridemia and type 2 diabetes (TRIAGE), in the United States.

In November 2019, Afimmune Ltd.

announced positive results from an exploratory Phase 2 study of epeleuton in patients with NAFLD in which the molecule decreased triglycerides, improved glycemic control, and decreased markers of inflammation.

In August 2020, Afimmune reported Ph2a study results of epeleuton in patients with NAFLD.

Although epeleuton failed to meet the primary endpoint to demonstrate effects on liver enzyme elevation, it demonstrated significant reduction of triglycerides, HbA1c and potential for CV risk reduction.

In September 2020, Afimmune announced the start of TRIglyceride And Glucose control with Epeleuton in Metabolic Syndrome Patients, or TRIAGE, a

Phase IIb study of epeleuton in patients with high triglycerides and type 2 diabetes to assess the safety and efficacy of orally administered epeleuton capsules vs placebo in the treatment of hypertriglyceridemia and type 2 diabetes.

The trial completed in May 2022 and results are expected in the fourth quarter of 2022.

Further, drugs in development that are expected to compete with VASCEPA if they are ultimately approved and commercialized, and the perceived safety and efficacy of such commercialized drugs or drug products, could have a negative impact on the perceived safety and efficacy of VASCEPA.

Based on prior communications from the U.S.

FDA, including communications in connection with its review of the ANCHOR indication for VASCEPA, it is our understanding that the U.S.

FDA is not prepared to approve any therapy for treatment of cardiovascular risk based on biomarker modification without cardiovascular outcomes study data, with the potential exception of therapies which lower LDL-cholesterol, depending on the circumstances.

FDA is not prepared to approve any therapy for treatment of CV risk based on biomarker modification without cardiovascular outcomes study data, with the potential exception of therapies which lower LDL-cholesterol, depending on the circumstances.

In particular, it is our understanding that the U.S.

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FDA did not change based on the REDUCE-IT study particularly in light of significant independence of the positive benefit demonstrated in the REDUCE-IT study from triglyceride levels and benefit from the REDUCE-IT study supporting that the positive effects of VASCEPA are unique to VASCEPA and extend beyond triglyceride reduction.

FDA were to change this position, it could potentially have a negative impact on us by making it easier for other products to achieve a cardiovascular risk reduction indication without the need in advance to conduct a long and expensive cardiovascular outcomes study.

FDA were to change this position, it could potentially have a negative impact on us by making it easier for other products to achieve a CV risk reduction indication without the need in advance to conduct a long and expensive CV outcomes study.

VASCEPA also faces competition from dietary supplement manufacturers marketing omega-3 products as nutritional supplements.

Such products are classified as food, not as prescription drugs or over-the-counter drugs, by the U.S.

FDA in the United States.

Most regulatory regimes outside the United States are similar in this regard.

FDA and other regulators.

Some of the promoters of such products have greater resources than us and are not restricted to the same standards as are prescription drugs with respect to promotional claims or manufacturing quality, consistency and subsequent product stability.

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FDA’s stringent regulatory oversight, as significant advantages versus omega-3 dietary supplements regardless of clinical study results and other scientific data.

Although VASCEPA is currently the only drug that is approved for cardiovascular risk reduction in Europe in the at-risk patient population studied in REDUCE-IT, and there is currently no other direct competition for Canada and the Middle East, consistent with the U.S., our competitors include large, well-established and experienced pharmaceutical companies, specialty and generic pharmaceutical companies, marketing companies, and specialized cardiovascular treatment companies and we have no experience as a company self-commercializing a product outside of the United States.

Consistent with the competitive landscape in the United States, our competitors outside of the United States include large, well-established and experienced pharmaceutical companies, specialty and generic pharmaceutical companies, marketing companies, and specialized cardiovascular treatment companies and we have no experience as a company self-commercializing a product outside of the United States.

Recent CV outcomes trials and meta-analyses with low and high dose omega-3 fatty acid mixtures containing DHA have not shown substantial benefit in patients receiving contemporary medical therapy, including statins.

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The STRENGTH trial of an omega-3 mixture studied at 4-grams per day also failed to demonstrate cardiovascular benefit.

As generic company competitors seek to compete with copies of VASCEPA in the United States and elsewhere we could face additional challenges to our patents and additional patent litigation.

As generic competitors seek to compete with VASCEPA in the United States and elsewhere we could face additional challenges to our patents and additional patent litigation.

The FDCA, as amended by the Drug Price Competition and Patent Term Restoration Act of 1984, as amended, or the Hatch-Waxman Amendments, permits the U.S.

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FDA approval for modifications of products previously approved by the U.S.

FDA, an applicant may submit a new drug application, or NDA, under Section 505(b)(2) of the FDCA (enacted as part of the Hatch-Waxman Amendments).

FDA, an applicant may submit a new drug application, or NDA, under Section 505(b)(2) of the FDCA (enacted as part of the Hatch-Waxman

This statutory provision permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference from the owner of the data.

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Accordingly, we received three-year exclusivity in connection with the approval of our sNDA for REDUCE-IT study results.

Such three-year exclusivity protection precludes, unless otherwise agreed, the U.S.

Such three-year exclusivity protection precluded the U.S.

FDA from approving a marketing application for an ANDA, a product candidate that the U.S.

FDA views as having the same conditions of approval as VASCEPA (for example, the same indication and/or other conditions of use), or a 505(b)(2) NDA submitted to the U.S.

FDA with VASCEPA as the reference product until December 13, 2022, three years from the date of U.S.

FDA with VASCEPA as the reference product until such protection expired on December 13, 2022, three years from the date of U.S.

FDA approval of the REDUCE-IT sNDA.

While this three-year exclusivity would generally prevent such an approval based on our REDUCE-IT indication during such time, it does not preclude tentative or final approval of an ANDA based on our MARINE indication.

FDA may accept and commence review of such REDUCE-IT-related applications during the three-year exclusivity period.

Such three-year exclusivity grant does not prevent a company from challenging the validity of REDUCE-IT patents during such period.

This three-year form of exclusivity may also not prevent the U.S.

FDA from approving an NDA that relies only on its own data to support the change or innovation.

Regulatory exclusivity is in addition to exclusivity afforded by issued patents related to VASCEPA.

We may also face challenges to the validity of our patents through a procedure known as inter partes review.

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Such proceedings may review the patentability of one or more claims in a patent on specified substantive grounds such as allegations that a claim is obvious on the basis of certain prior art.

We intend to vigorously enforce our intellectual property rights relating to VASCEPA, but we cannot predict the outcome of the pending lawsuits, any appeals, or any subsequently filed lawsuits or inter partes review.

We cannot predict the outcome of the pending lawsuits, any appeals, or any subsequently filed lawsuits or inter partes review.

Generally, if an ANDA filer meets the approval requirements for a generic version of VASCEPA to the satisfaction of the U.S.

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Generic versions of VASCEPA made available in the market, even if based on a MARINE indication, are often used to fill a prescription for any intended use of the drug.

If any approved ANDA filers are able to supply the product in significant commercial quantities, generic companies could introduce generic versions of VASCEPA in the market, as did Hikma in November 2020, Dr.

Reddy's in June 2021, Apotex in January 2022 and Teva for the 0.5-gram capsule only in September 2022.

If any approved ANDA filers are able to supply the product in significant commercial quantities, generic companies could introduce generic versions of VASCEPA in the market, as Hikma, Dr.

Reddy's, Apotex and Teva have done.

Although any such introduction of a generic version of VASCEPA would also be subject to any litigation settlement terms and patent infringement claims (including any new claims and those that may then be subject to an appeal), pursuing such litigation may be prohibitively costly or could put a substantial constraint on our resources.

On July 9, 2021, President Biden issued an executive order directing the U.S.

FDA to, among other things, continue to clarify and improve the approval framework for generic drugs and identify and address any efforts to impede generic drug competition.

Any significant degree of generic market entry would limit our U.S.

sales, which would have a significant adverse impact on our business and results of operations.

In addition, even if a competitor’s effort to introduce a generic product is ultimately unsuccessful, the perception that such development is in progress and/or news related to such progress or news related to litigation outcomes could materially affect the reputation of VASCEPA or the perceived value of our company and our stock price.

The generic market entries beginning in 2020 have limited our U.S.

sales, and had an adverse impact on our business and results of operations.

In addition, generic market entry, whether limited to its approved indication or not, can create market disruption which leads to an overall slowing of market growth regardless of whether the net price of the generic entry is higher or lower than the net price of the branded drug.

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While an authorized generic could be profitable, the market opportunity for growth from an authorized generic is likely less than from promotion of a branded drug, and as such we have not launched an authorized generic version of VASCEPA to date, but may elect to do so in the future.

The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, often requires considerable advanced planning and long-term financial commitments to ensure sufficient capacity is available when needed.

One of our generic competitors has filed a lawsuit against us claiming we have engaged in anticompetitive practices related to our building of adequate supply for our needs and government agencies are investigating our business as it relates to the supply of the active pharmaceutical ingredient in VASCEPA.

The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture.

It often requires considerable advanced planning and long-term financial commitments to ensure sufficient capacity is available when needed.

Certain generic competitors filed lawsuits against us claiming we have engaged in anticompetitive practices related to our building of adequate supply for our needs, and government agencies are investigating our business as it relates to the supply of the active pharmaceutical ingredient in VASCEPA.

Consumer lawsuits with similar allegations have also been filed.

This dynamic and resulting regulatory scrutiny could be costly for us and could negatively and materially interfere with our business plans.

The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, often requires considerable advanced planning and necessitates long-term financial commitments to ensure sufficient capacity is available when needed.

We have invested over a decade of resources and expenses to develop with our third-party, active pharmaceutical ingredient supply chain the technical knowhow, manufacturing processes and related regulatory approvals that have helped enable our suppliers to supply our clinical and commercial needs globally.

As has been a practice in the generic pharmaceutical industry, on April 27, 2021, Dr.

The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, and often requires considerable advanced planning and necessitates long-term financial commitments to ensure sufficient capacity is available when needed.

We have invested over a decade of resources and expenses to develop active pharmaceutical ingredient, or API, with our third-party supplier, and to otherwise build our supply chain, improve our technical knowhow, establish manufacturing processes and obtain related regulatory approvals to help enable our suppliers to supply our clinical and commercial needs globally.

Despite such efforts, the stability of the supply chain is largely out of our control and is subject to market and supply volatility and the actions of third parties.

Any disruption to the supply chain, including the manufacturing processes and availability of API, would be disruptive to our business and would have a negative impact on our results of operations.

In April 2021, Dr.

Reddy’s filed a complaint against us in the United States District Court District of New Jersey (case no.

2:21-cv-10309) alleging various antitrust violations stemming from alleged anticompetitive practices related to the supply of active pharmaceutical ingredient of VASCEPA.

2:21-cv-10309) alleging various antitrust violations stemming from alleged anticompetitive practices related to the supply of API of VASCEPA.

Damages sought include recovery for alleged economic harm to Dr.

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Reddy’s.

Consumer group lawsuits followed claiming similar violations and alleging, for example, that such alleged violations resulted in higher prices to consumers.

Consumer group lawsuits followed claiming similar violations and alleging that such alleged violations resulted in higher prices to consumers.

In addition, in February 2023, Hikma filed a complaint against us in the United States District Court District of New Jersey (case no.

3:23-cv-01016) making allegations consistent with the Dr.

Reddy's complaint.

Such litigation can be lengthy, costly and could materially affect and disrupt our business.

We believe we have valid defenses and will vigorously defend against the claims but cannot predict the outcome.

We have also received a civil investigative demand from the U.S.

FTC and a subpoena from the New York Attorney General with respect to practices relating to our supply of the active pharmaceutical ingredient in VASCEPA.

We believe such contact from the governments may have been prompted by a generic competitor.

In addition, as noted above, we have also received a CID from the U.S.

FTC and a subpoena from the New York Attorney General with respect to practices relating to our supply of the API in VASCEPA.

The government inquiries require us to produce documents and answer related questions relevant to specified time periods.

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Such investigations can be lengthy, costly and could materially affect and disrupt our business.

We cannot predict when these investigations will be resolved, the outcome

of the investigations or their potential impact on our business.

We cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

If a government determines that we have violated antitrust law, we could be subject to significant civil fines and penalties.

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Omega-3 fatty acids are also marketed by other companies as non-prescription dietary supplements.

As a result, in the U.S.

VASCEPA is subject to non-prescription competition and consumer substitution.

As a result, in the U.S., VASCEPA is subject to non-prescription competition and consumer substitution.

Our only product, VASCEPA, is a prescription-only form of EPA, an omega-3 fatty acid in ethyl ester form.

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In addition, the U.S.

FDA has not yet enforced to the full extent of its regulatory authority what we view as illegal claims made by certain omega-3 fatty acid product manufacturers to the extent we believe appropriate under applicable law and regulations, for example, claims that certain of such chemically altered products are dietary supplements and that certain of such products reduce triglyceride levels or could reduce cardiovascular risk.

FDA has not yet enforced to the full extent of its regulatory authority what we view as illegal claims made by certain omega-3 fatty acid product manufacturers to the extent we believe appropriate under applicable law and regulations, for example, claims that certain of such chemically-altered products are dietary supplements and that certain of such products reduce triglyceride levels or could reduce CV risk.

Also, for over a decade, subject to certain limitations, the U.S.

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FDA enforcement activity, to make claims that suggest or imply treatment of cardiovascular disease.

These factors enable dietary supplements to compete with VASCEPA to a certain degree.

Although we have taken steps to address these competitive issues, and plan to continue to do so vigorously, we may not be successful in such efforts.

For example, on October 29, 2018, we filed two lawsuits in U.S.

federal court, each against a different dietary supplement company for unlawfully using the results from the REDUCE-IT cardiovascular outcomes study to falsely and deceptively claim that their omega-3 dietary supplement products are effective in reducing cardiovascular risk.

The defendants in the cases were Omax Health, Inc., or Omax, and The Coromega Company, Inc., or Coromega.

In April 2019, based on the strength of our case and available legal remedies, Omax and Coromega settled these litigations under terms by which Omax and Coromega agreed to substantially all the demands in our complaints.

Under the settlements, Coromega and Omax agreed to publicly correct their prior statements that wrongly suggested the REDUCE-IT cardiovascular outcomes trial supports the safety and efficacy of omega-3 dietary supplements.

Each dietary supplement company also acknowledged that as a general matter under federal law dietary supplements may be lawfully marketed to supplement the diet, but they cannot be lawfully marketed to treat, mitigate, or prevent disease, such as cardiovascular disease.

Similarly, on August 30, 2017, we filed a lawsuit with the United States International Trade Commission, or the ITC, against manufacturers, importers, and distributors of products containing synthetically produced omega-3 products in ethyl ester or re-esterified triglyceride form that contain more EPA than DHA or any other single component for use in or as dietary supplements.

The lawsuit sought an investigation by the ITC regarding potentially unfair methods of competition and unfair acts involving the importation and sale of articles in the United States that injure or threaten injury to a domestic industry.

In October 2017, the ITC determined to not institute our requested investigation.

We appealed this determination to the U.S.

Federal Circuit, but that court upheld ITC’s determination.

On July 30, 2019, we filed a petition with the U.S.

Supreme Court seeking to appeal the Federal Circuit decision, which petition was denied on December 9, 2019, ending this litigation.

We have also engaged with U.S.

FDA on the topic of synthetically produced omega-3 products through the citizen’s petition process and otherwise.

In addition, to the extent the net price of VASCEPA to patients after insurance and offered discounts is significantly higher than the prices of commercially available omega-3 fatty acids marketed by other companies as dietary supplements (through the lack of coverage by insurers or otherwise), physicians and pharmacists may recommend these retail alternatives instead of writing or filling prescriptions for VASCEPA or patients may elect on their own to take commercially available omega-3 fatty acids.

These factors enable dietary supplements to compete with VASCEPA.

We may not be successful in such efforts, or such efforts may prove too costly to be effective.

In addition, the net price of VASCEPA to patients even after insurance reimbursement and offered discounts could be significantly higher than the prices of commercially available omega-3 fatty acids marketed by other companies as dietary supplements (through the lack of coverage by insurers or otherwise).

Physicians and pharmacists may recommend these retail alternatives instead of writing or filling prescriptions for VASCEPA or patients may elect on their own to take commercially available omega-3 fatty acids.

Also, insurance plans may increasingly impose policies that directly or indirectly favor supplement use over VASCEPA.

While VASCEPA is priced comparatively with, or in some cases lower than, many competing treatments, particularly when taking into account insurance coverage, such pricing might not be sufficient for healthcare providers or patients to elect VASCEPA over alternative treatments that may be perceived as less expense or more convenient to access.

VASCEPA pricing might not be sufficient for healthcare providers or patients to elect VASCEPA over alternative treatments that may be perceived as less expense or more convenient to access.

If healthcare providers or patients favor dietary supplements over prescribing VASCEPA, we may be constrained in how we price our product or VASCEPA’s market acceptance may be less than expected, which would have a negative impact on our revenues and results of operations.

* The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including adequacy of product reimbursement, which can vary from country to country.

If we are unable to realize product reimbursement rates at reasonable levels, or at all, patient access to VASCEPA may be limited.

There can be no assurance as to the market for VASCEPA outside the United States.

For example, despite having received EC approval to commercialize VAZKEPA in Europe and through our partner, Edding, marketing approval for VASCEPA in Hong Kong as well as we expect to obtain through Edding, marketing approval for VASCEPA in Mainland China, Macau and Taiwan, applicable regulatory agencies may impose restrictions on the product’s conditions for use, distribution or marketing and in some cases may impose ongoing requirements for post-market surveillance, post-approval studies or clinical trials.

In some foreign countries, including major markets in Europe, the pricing of prescription pharmaceuticals is subject to governmental control.

As a result of the negotiation outcome, we have discontinued our German operations as of September 1, 2022.

Further, in certain European countries, securing product reimbursement is a requisite to commercial launch.

To obtain reimbursement or pricing approval in some countries, we may be required to conduct a pharmacoeconomic study that compares the cost-effectiveness of VASCEPA to other available therapies.

Such pharmacoeconomic studies can be costly and the results uncertain.

The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted at this time.

Our business could be harmed if reimbursement of our products is unavailable, delayed or limited in scope or amount or if pricing is set at unsatisfactory levels.

We or our partners may even choose to not proceed with marketing VASCEPA in a market, even after a regulatory approval, due to negative commercial dynamics.

If any of these market dynamics exist, the commercial potential in these territories for our product would suffer.

Our products and marketing efforts are subject to extensive post-approval government regulation.

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FDA rules in addition to other applicable federal and local laws in the United States and in other countries.

The result of our First Amendment litigation and settlement may cause the government to scrutinize our promotional efforts or otherwise monitor our business more closely.

The result of our litigation and settlement with the U.S.

FDA, as discussed above, may cause the government to scrutinize our promotional efforts or otherwise monitor our business more closely.

Industry-sponsored scientific and educational activities also must comply with U.S.

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FDA approval for product and manufacturing changes, depending on the nature of the change.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are subject to periodic unannounced inspections by the U.S.

Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are also subject to periodic unannounced inspections by the U.S.

FDA and state agencies for compliance with cGMP requirements.

In addition, under the Food and Drug Omnibus Reform Act of 2022, or FDORA, sponsors of approved drugs and biologics must provide 6 months’

notice to the FDA of any changes in marketing status, such as the withdrawal of a drug, and failure to do so could result in the FDA placing the product on a list of discontinued products, which would revoke the product’s ability to be marketed.

We participate in the U.S.

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Similar requirements exist in many of these areas in other countries.

Depending on the circumstances, failure to meet post-approval requirements can result in criminal prosecution, fines or other penalties, injunctions, recall or seizure of products, total or partial suspension of production, denial or withdrawal of pre-marketing product approvals, or refusal to allow us to enter into supply contracts, including government contracts.

product approvals, or refusal to allow us to enter into supply contracts, including government contracts.

We may also be held responsible for the non-compliance of our partners, such as our former co-promotion partner Kowa America.

As discussed above, in June 2020, we received a CID from the DOJ informing us that the DOJ is investigating whether aspects of our promotional speaker programs and copayment waiver programs during the period from January 1, 2015 to the present violated the U.S.

Anti-Kickback

Statute and the U.S.

Anti-Kickback Statute and the U.S.

FCA in relation to the sale and marketing of VASCEPA by us and our previous co-marketing partner, Kowa America.

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The inquiries require us to produce documents and answer written questions, or interrogatories, relevant to specified time periods.

We are cooperating with the government.

We cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

Such investigations can be lengthy, costly and could materially affect and disrupt our business.

If the government determines that we have violated the U.S.

Anti-Kickback Statute, the FCA or antitrust regulations, we could be subject to significant civil and criminal fines and penalties.

Anti-Kickback Statute, the FCA or antitrust regulations, we could be subject to significant civil and criminal fines and penalties, and our reputation may be harmed.

In addition, even if we comply with U.S.

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and foreign governments, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce healthcare costs may adversely affect our ability to set prices for our products which we believe are fair, and our ability to generate revenues and achieve and maintain profitability.

Specifically, in the United States and in some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes to the healthcare system in ways that could affect our ability to sell our products profitably.

For example, on August 2, 2011, the Budget Control Act of 2011, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals for spending reductions.

The Joint Select Committee did not achieve a targeted deficit reduction, which triggered the legislation’s automatic reductions.

In concert with subsequent legislation, this has resulted in aggregate reductions to Medicare payments to providers of, on average, 2% per fiscal year through 2030 with the exception of a temporary suspension from May 1, 2020 through March 31, 2022 due to the COVID-19 pandemic.

Following the suspension, a 1% payment reduction occurred from April 1, 2022 through June 30, 2022, and the 2% payment reduction resumed on July 1, 2022.

These cuts reduce reimbursement payments related to our products, which could potentially negatively impact our revenue.

Also for example, the ACA has substantially changed the way healthcare is financed by both governmental and private insurers and has significantly impacted the U.S.

pharmaceutical industry.

Among other cost-containment measures, the ACA establishes:

an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs and biologic agents;

a new Medicare Part D coverage gap discount program, in which pharmaceutical manufacturers who wish to have their drugs covered under Part D must offer discounts to eligible beneficiaries during their coverage gap period;

a new formula that increases the rebates a manufacturer must pay under the Medicaid Drug Rebate Program and extends the Medicaid Drug Rebate Program to individuals enrolled in Medicaid managed care organizations.

There has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.

Specifically, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs.

At a federal level, President Biden signed an Executive Order on July 9, 2021 affirming the administration's policy to (i) support legislative reforms that would lower the prices of prescription drug and biologics, including by allowing Medicare to negotiate drug prices, by imposing inflation caps, and, by supporting the development and market entry of lower-cost generic drugs and biosimilars;

and (ii) support the enactment of a public health insurance option.

Among other things, the Executive Order also directs HHS to provide a report on actions to combat excessive pricing of prescription drugs, enhance the domestic drug supply chain, reduce the price that the federal government pays for drugs, and address price gouging in the industry;

and directs the FDA to work with states and Indian Tribes that propose to develop section

804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and the FDA's implementing regulations.

FDA released such implementing regulations on September 24, 2020, which went into effect on November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.

On September 25, 2020, CMS stated drugs imported by states under this rule will not be eligible for federal rebates under Section 1927 of the Social Security Act and manufacturers would not report these drugs for "best price" or Average Manufacturer Price purposes.

Since these drugs are not considered covered outpatient drugs, CMS further stated it will not publish a National Average Drug Acquisition Cost for these drugs.

If implemented, importation of drugs from Canada may materially and adversely affect the price we receive for any of our product candidates.

Further, on November 20, 2020 CMS issued an Interim Final Rule implementing the Most Favored Nation, or MFN, Model under which Medicare Part B reimbursement rates would have been calculated for certain drugs and biologicals based on the lowest price drug manufacturers receive in Organization for Economic Cooperation and Development countries with a similar gross domestic product per capita.

However, on December 29, 2021 CMS rescinded the Most Favored Nations rule.

Additionally, on November 30, 2020, HHS published a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026.

In August 2022, the Inflation Reduction Act of 2022, or the IRA, was signed into law.

The IRA includes several provisions that will impact our business to varying degrees, including provisions that create a $2,000 out-of-pocket cap for Medicare Part D beneficiaries, impose new manufacturer financial liability on all drugs and biologics without generic or biosimilar competition, require companies to pay rebates to Medicare for drug prices that increase faster than inflation, and delay the rebate rule that would require pass through of pharmacy benefit manager rebates to beneficiaries.

The effect of IRA on our business and the healthcare industry in general is not yet known.

Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, both the Biden administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

In addition, it is time-consuming and expensive for us to go through the process of seeking coverage and reimbursement from Medicare and private payors.

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In addition, increasing emphasis on managed care in the United States will continue to put pressure on the pricing of pharmaceutical products.

For example, proposals are being considered to expand the use of dietary supplements in addition to or in place of drugs in government and private payor plans.

Proposals are being considered to expand the use of dietary supplements in addition to or in place of drugs in government and private payor plans.

In addition, cost control initiatives could decrease the price that we or any potential collaborators could receive for any of our future products and could adversely affect our profitability.

These and similar regulatory dynamics, including the recent entry of generic versions of VASCEPA into the market, and the potential for additional generic versions in the near term, can affect our ability to commercialize VASCEPA on commercially reasonable terms and limit the commercial value of VASCEPA.

These and similar regulatory dynamics, including the entry of generic versions of VASCEPA into the market, and the potential for additional generic versions in the near term, can affect our ability to commercialize VASCEPA on commercially reasonable terms and limit the commercial value of VASCEPA.

If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

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The ACA made significant changes to the Medicaid Drug Rebate program.

CMS issued a final regulation, which became effective on April 1, 2016, to implement the changes to the Medicaid Drug Rebate program under the ACA.

CMS issued a final regulation, which became effective in 2016, to implement the changes to the Medicaid Drug Rebate program under the ACA.

The issuance of the final regulation has increased and will continue to increase our costs and the complexity of compliance, has been and will continue to be time-consuming to implement, and could have a material adverse effect on our results of operations, particularly if CMS challenges the approach we take in our implementation of the final regulation.

Federal law requires that any company that participates in the Medicaid Drug Rebate program also participate in the Public Health Service’s 340B drug pricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.

The 340B program requires participating manufacturers to agree to charge statutorily defined covered entities no

more than the 340B “ceiling price”

The 340B program requires participating manufacturers to agree to charge statutorily defined covered entities no more than the 340B “ceiling price”

for the manufacturer’s covered outpatient drugs.

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Some third-party payor benefit packages restrict reimbursement, charge copayments to patients, or do not provide coverage for specific drugs or drug classes.

In addition, certain U.S.

based healthcare providers are moving toward a managed care system in which such providers contract to provide comprehensive healthcare services, including prescription drugs, for a fixed cost per person.

We are unable to predict the reimbursement policies employed by third-party healthcare payors.

In addition, certain U.S.-based healthcare providers are moving toward a managed care system in which such providers contract to provide comprehensive healthcare services, including prescription drugs, for a fixed cost per person.

We are unable to predict the reimbursement policies employed by third-party healthcare payors which may not be favorable to us.

We expect to experience pricing and reimbursement pressures in connection with the sale of our products due to the trend toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative and executive proposals, as well as the availability of generic versions of VASCEPA.

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Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.

Certain provisions of the ACA have been subject to judicial challenges, as well as efforts to repeal or replace them or to alter their interpretation or implementation.

Multiple Executive Orders were signed during the Trump administration which were designed to delay the implementation of certain provisions of the ACA or otherwise circumvent some of the requirements for health insurance mandated by the ACA.

For example, the previous administration terminated the cost-sharing subsidies under the ACA.

Nineteen state Attorneys General filed suit to stop the administration from terminating the subsidies, but on July 18, 2018, the U.S.

District Court for the Northern District of California dismissed the case without prejudice.

Further, on June 14, 2018, U.S.

Court of Appeals for the Federal Circuit ruled that, due to Congressional appropriations riders that prohibited the HHS from paying out more in risk corridor payments than it collected, HHS was not required to pay more than $12.0 billion in ACA risk corridor payments owed to insurers under the risk corridor formula.

On November 6, 2018, the Federal Circuit declined to rehear the case en banc.

This decision was appealed to the U.S.

Supreme Court, which on April 27, 2020, reversed the U.S.

Court of Appeals for the Federal Circuit’s decision and remanded the case to the U.S.

Court of Federal Claims, concluding the government has an obligation to pay these risk corridor payments under the relevant formula.

It is not clear what effect this result will have on our business, but we will continue to monitor any developments.

Moreover, the Tax Act included a provision that eliminated the tax-based shared responsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of 1986, commonly referred to as the “individual mandate,”

effective January 1, 2019.

The Bipartisan Budget Act of 2018, or the BBA, among other things, amends the ACA to create a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% (an increase from 50% effective as of January 1, 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.

Under the Trump administration, CMS issued regulations that gave states greater flexibility, starting in 2020, in the identification of the essential health benefits benchmarks for non-grandfathered individual and small group market health insurance coverage, including plans sold through the health insurance exchanges established under the ACA.

On December 14, 2018, the U.S.

District Court for the Northern District of Texas ruled (i) that the “individual mandate”

was unconstitutional as a result of the associated tax penalty being repealed by Congress as part of the Tax Act;

and (ii) the individual mandate is not severable from the rest of the ACA, as a result the entire ACA is invalid.

On December 18, 2019, the U.S.

Court of Appeals for the Fifth Circuit affirmed the district court’s decision that the individual mandate is unconstitutional, but remanded the case to the district court to reconsider the severability question.

On March 2, 2020, the U.S.

Supreme Court granted the petitions for writs of certiorari to review this case and held oral arguments on November 10, 2020.

On June 17, 2021, the U.S.

Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Prior to the Supreme Court’s decision, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021 through August 15, 2021 for the purpose of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is unclear how other healthcare reform measures of the Biden administration or other efforts, if any, to challenge, repeal or replace the ACA will impact our business.

In addition, there have been several changes to the 340B drug pricing program, which imposes ceilings on prices that drug manufacturers can charge for medications sold to certain health care facilities.

On December 27, 2018, the District Court for the District of Columbia invalidated a reimbursement formula change under the 340B drug pricing program, and CMS subsequently altered the FYs 2019 and 2018 reimbursement formula on specified covered outpatient drugs, or SCODs.

The court ruled this change was not an “adjustment”

which was within the Secretary’s discretion to make but was instead a fundamental change in the reimbursement calculation.

However, on July 31, 2020, the U.S.

Court of Appeals for the District of Columbia Circuit overturned the district court’s decision and found that the changes were within the Secretary’s authority.

On September 14, 2020, the plaintiffs-appellees filed a Petition for Rehearing En Banc (i.e., before the full court), but was denied on October 16, 2020.

On February 10, 2021, plaintiffs-appellees filed a writ of certiorari with the U.S.

Supreme Court.

On June 15, 2022, the Supreme Court unanimously reversed the Court of Appeals' decision, holding that HHS's 2018 and 2019 reimbursement rates for 340B hospitals were contrary to

the statute and unlawful.

We continue to review developments impacting the 340B program.

It is unclear how these developments could affect covered hospitals who might purchase our future products and affect the rates we may charge such facilities for our approved products in the future, if any.

We expect that the healthcare reform measures that have been adopted and may be adopted in the future, may result in more rigorous coverage criteria, and new payment methodologies, and in additional downward pressure on coverage and payment and the price that we receive for any approved product, and could seriously harm our future revenues.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private third-party payors.

and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any products for which we obtain marketing approval.

Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example:

(i) changes to our manufacturing arrangements;

(ii) additions or modifications to product labeling;

(iii) the recall or discontinuation of our products;

or (iv) additional record-keeping requirements.

If any such changes were to be imposed, they could adversely affect the operation of our business.

There has been increasing legislative and enforcement interest in the United States with respect to drug pricing practices.

Specifically, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.

The Inflation Reduction Act of 2022, or IRA, includes several provisions that may impact our business to varying degrees, including provisions that that reduce the out-of-pocket spending cap for Medicare Part D beneficiaries from $7,050 to $2,000 starting in 2025, thereby effectively eliminating the coverage gap, impose new manufacturer financial liability on all drugs in Medicare Part D, allow the U.S.

government to negotiate Medicare Part B and Part D pricing for certain high-cost drugs and biologics without generic or biosimilar competition, require companies to pay rebates to Medicare for drug prices that increase faster than inflation, and delay until January 1, 2032 the implementation of the HHS rebate rule that that would have limited the fees that pharmacy benefit managers can charge.

Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one rare disease designation and for which the only approved indication is for that disease or condition.

If a product receives multiple rare disease designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

The effect of IRA on our business and the healthcare industry in general is not yet known.

In addition, President Biden has issued multiple executive orders that have sought to reduce prescription drug costs.

In February 2023, HHS also issued a proposal in response to an October 2022 executive order from President Biden that includes a proposed prescription drug pricing model that will test whether targeted Medicare payment adjustments will sufficiently incentivize manufacturers to complete confirmatory trials for drugs approved through FDA’s accelerated approval pathway.

The continuing efforts of the government, insurance companies, managed care organizations and other payers of healthcare services to contain or reduce costs of healthcare may adversely affect:

the demand for any of our product candidates, if approved;

the ability to set a price that we believe is fair for any of our product candidates, if approved;

our ability to generate revenues and achieve or maintain profitability;

the level of taxes that we are required to pay;

the availability of capital.

There have been, and likely will continue to be, legislative and regulatory proposals at the foreign, federal and state levels directed at broadening the availability of healthcare and containing or lowering the cost of healthcare.

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Claims that we have violated individuals’

privacy rights, failed to comply with data protection laws, or breached our contractual obligations, even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.

European data collection is governed by restrictive regulations governing the use, processing and cross-border transfer of personal information.

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The GDPR imposes several requirements relating to the legal basis for processing personal data which may include the consent of the individuals to whom the personal data relates, the information provided to the individuals and the security and confidentiality of the personal data.

The GDPR also imposes strict rules on the transfer of personal data out of the EEA to the United States.

The GDPR also imposes strict rules on the transfer of personal data out of the EEA to third countries, including the United States.

A decision by the Court of Justice of the European Union, or CJEU, in 2020 invalidated the EU-U.S.

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The new forms of standard contractual clauses have replaced the standard contractual clauses that were adopted previously under the Data Protection Directive.

We will be required to transition to the new forms of standard contractual clauses and doing so will require significant effort and cost.

The new standard contractual clauses may also impact our business as companies based in Europe may be reluctant to utilize the new clauses to legitimize transfers of personal information to third countries given the burdensome requirements of transfer impact assessments and the substantial obligations that the new standard contractual clauses impose upon exporters.

Failure to comply with the requirements of the GDPR, and the related

national data protection laws of the EEA Member States may result in restrictions against regulatory approval in the EEA or substantial fines for breaches of the data protection rules.

They require a case-by-case assessment of the law in the recipient country to ensure it provides “essentially equivalent”

protections to safeguard the transferred personal data as the EEA, and require businesses to adopt supplementary measures if such standard is not met.

The new SCCs do not apply to the UK, but the UK Information Commissioner’s Office has published its own transfer mechanism, the International Data Transfer Agreement, or UK IDTA, which entered into force on March 21, 2022, and enables data transfers originating from the UK.

It requires a similar assessment of the data protection provided in the importer’s country.

We will be required to transition to the new forms of transfer mechanisms and doing so will require significant effort and cost.

The new transfer

mechanisms may also impact our business as companies based in Europe may be reluctant to utilize the new clauses to legitimize transfers of personal information to third countries given the burdensome requirements of transfer impact assessments and the substantial obligations that the new standard contractual clauses impose upon exporters.

Failure to comply with the requirements of the GDPR or the UK GDPR, and the related national data protection laws of the EEA Member States or the UK may result in substantial fines.

The GDPR may impose additional responsibility and liability in relation to personal data that we process and we may be required to put in place additional mechanisms ensuring compliance with these and/or new data protection rules.

This may be onerous and adversely affect our business, financial condition, prospects and results of operations.

This may be costly, onerous and adversely affect our business, financial condition, prospects and results of operations.

FDA, other regulatory agencies and industry organizations strictly regulate the promotional claims that may be made about prescription products and promotional efforts such as speaker programs.

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Even though we received U.S.

FDA marketing approval for VASCEPA for the MARINE indication and for cardiovascular risk reduction based on the REDUCE-IT study, and our settlement with the U.S.

FDA marketing approval for VASCEPA for the MARINE indication and for the REDUCE-IT indication, and our settlement with the U.S.

FDA affords us a degree of protection for other promotional efforts, physicians may still prescribe VASCEPA to their patients for use in the treatment of conditions that are not included as part of the indication statement in our U.S.

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Such suits may also result in related shareholder lawsuits, which are also costly to defend.

In June 2020, we received a CID from the DOJ informing us that the DOJ is investigating whether aspects of our promotional speaker programs and copayment waiver program during the period from January 1, 2015 to the present violated the U.S.

Anti-Kickback Statute and the FCA in relation to the sale and marketing of VASCEPA by us and our previous co-marketing partner, Kowa America.

Similarly, in March 2021, the FTC issued a CID to us in connection with the FTC’s investigation of whether we have engaged in, or are engaging in, anticompetitive practices or unfair methods of competition relating to VASCEPA.

The New York State attorney general similarly issued a subpoena to us regarding the same subject matter on which the FTC CID is focused.

The inquiries require us to produce documents and answer written questions, or interrogatories, relevant to specified time periods.

We are cooperating with the government.

We cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

For example, the June 2020 CIDs from the DOJ informing us that the DOJ is investigating whether aspects of our promotional speaker programs and copayment waiver program violated the U.S.

Anti-Kickback Statute and from the FCA relating to the sale and marketing of VASCEPA by us and our previous co-marketing partner, Kowa America, as well as the March 2021 CID from the FTC in connection with the FTC’s investigation of whether we have engaged in, or are engaging in, anticompetitive practices or unfair methods of competition relating to VASCEPA require us to produce documents and answer written questions, or interrogatories, relevant to specified time periods.

The subpoena from the New York State attorney general covers the same subject matter on which the FTC CID is focused.

Such investigations can be lengthy, costly and could materially affect and disrupt our business.

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The failure of clinical trials to demonstrate safety and efficacy for our desired indications could harm the development of that product candidate as well as other product candidates, and our business and results of operations would suffer.

For example, during the public advisory committee meeting held by U.S.

FDA as part of its review of our ANCHOR data and sNDA in October 2013, a discussion regarding observed, nominally statistically significant changes from baseline in an adverse direction, while on background statin therapy, in certain lipid parameters, including LDL cholesterol and triglycerides, in the placebo group, raised questions about the possibility that the light liquid paraffin oil, or mineral oil, placebo used in the ANCHOR trial and then in use in the REDUCE-IT trial might not be biologically inert and might be viewed as artificially exaggerating the clinical effect of VASCEPA when measured against placebo.

Ultimately, in 2012, before the U.S.

FDA approval of VASCEPA after review of the MARINE and ANCHOR trials and consideration of other data regarding mineral oil, no strong evidence for biological activity of mineral oil was identified by the agency.

It was ultimately concluded that the between-group differences likely provided the most appropriate descriptions of the treatment effect of VASCEPA and that whatever factor(s) led to the within-group changes over time in the placebo group were likely randomly distributed to all treatment groups.

Thus, the U.S.

FDA approved VASCEPA for use in the MARINE indication in July 2012, U.S.

FDA did not dispute the veracity of the ANCHOR trial data and, in connection with the March 2016 agreement we reached with the U.S.

FDA allowing us to promote the results of the ANCHOR study, the U.S.

FDA did not seek to require that we include any qualification related to this earlier question regarding the mineral oil placebo.

In addition, in connection with U.S.

In connection with U.S.

FDA’s review of REDUCE-IT data and sNDA in 2019, the agency determined that an interaction between mineral oil and statins leading to decreased absorption of statins cannot be excluded when the two are co-administered as could have been the case in some patients in REDUCE-IT and that, in the agency’s view, indirect evidence suggested the presence of a potential inhibitory effect on statin absorption by mineral oil.

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The discovery of previously unknown problems with a clinical trial or product, or in connection with the manufacturer of products, may result in regulatory issues that prevent proposed future approvals of a product and/or restrictions on that product or manufacturer, including withdrawal of an indication or the product from the market, which would have a negative impact on our potential revenue stream.

*As we continue to build our infrastructure for commercializing VASCEPA, we may encounter difficulties in managing the scale of our operations successfully.

The process of establishing, maintaining, expanding and streamlining a commercial infrastructure is difficult, expensive and time-consuming.

In June 2022, we implemented a cost and organizational restructuring plan, which included a further reduction to our U.S.

commercial team from approximately 300 sales representatives to approximately 75 sales representatives.

Our sales team promotes VASCEPA to a targeted group of physicians and other healthcare professionals in select geographies in the United States who recognize the potential benefit to patients and is not large enough to call upon all physicians.

As we continue to scale our infrastructure for commercializing VASCEPA based on market dynamics for VASCEPA in the United States and commercial initiatives and plans for VAZKEPA in Europe and other parts of the world, we may encounter difficulties in managing the size and adaptability of our operations successfully.

The process of establishing, maintaining, expanding and streamlining a commercial infrastructure is difficult, expensive and time consuming, particularly when such efforts need to adapt to changing market and business dynamics.

We implemented cost and organizational restructuring plans, which included a reduction to our U.S.

commercial team to approximately 75 sales representatives by the end of 2022.

Our sales team promotes VASCEPA to a targeted group of physicians and other healthcare professionals in select geographies in the United States who recognize the potential benefit to patients, and this team is not large enough to call upon a sufficient number of physicians.

In addition to sales force reductions in the United States, we continue to work on our own and with our international partners to support regulatory efforts outside the United States based on REDUCE-IT results.

As our operations expand with the anticipated growth of our product sales, we expect that we will need to manage additional relationships with various collaborative partners, suppliers and other third parties.

If we are successful in obtaining sufficient

approvals and adequate pricing and reimbursement levels in major markets in Europe and elsewhere, we will need to ensure that our operations are adequate to support a commercial launch and continued promotion.

Although we are preparing for growth in Europe and elsewhere by expanding our infrastructure, we are operating with streamlined teams and will need to expand internally and we expect that we will need to manage additional relationships with various collaborative partners, suppliers and other third parties.

Future growth and streamlining efforts will impose significant added responsibilities on members of management, including the need to identify, recruit, maintain and integrate the right number of employees.

For example, in Europe we have built out our team subsequent to EC approval of the marketing authorization acceptance in 2021, with plans to continue to expand our European staff as deemed appropriate on a country by country basis.

In Europe we have built out our team subsequent to EC approval of the marketing authorization acceptance in 2021, with plans to continue to expand our European staff as deemed appropriate on a country by country basis.

The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted at this time.

While we believe that we have strong arguments regarding the cost effectiveness of VAZKEPA, the success of such reimbursement negotiations could have a significant impact on our ability to hire and retain personnel and realize the commercial opportunity of VAZKEPA in Europe.

Our future financial performance and our ability to commercialize VASCEPA and to compete effectively will depend, in part, on our ability to manage our future growth effectively, and such efforts may be disrupted by ongoing or reinstated COVID-19 protocols.

Our future financial performance and our ability to commercialize VASCEPA and to compete effectively will depend, in part, on our ability to manage our future growth effectively.

To that end, we must be able to manage our development efforts effectively, and hire, train, integrate and retain an appropriate level of management, administrative and sales and marketing personnel and have limited experience managing a commercial organization.

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Our life-cycle management, in large part, currently depends on our ability to develop, obtain regulatory approval and commercialize a fixed-dose combination of VASCEPA and yet to be disclosed statins.

Specifically, our drug development efforts are subject to the risks and uncertainties inherent in any drug development program.

Due to the risks and uncertainties involved in progressing through development and bioequivalence or even potential additional trials (as may be required by specific regulatory agencies), and the time and cost involved in obtaining regulatory approvals, among other factors, we cannot reasonably estimate the timing, completion dates and costs, or range of costs, of our drug development program, or of the successful development of any particular fixed-dose combination.

Our life-cycle management is substantially dependent on our ability to develop, obtain regulatory approval and commercialize a fixed-dose combination of VASCEPA and yet to be disclosed statins.

Due to the risks and uncertainties involved in progressing through development and bioequivalence or even potential additional trials (as may be required by specific regulatory agencies), and the time and cost involved in obtaining regulatory approvals, we cannot reasonably estimate the timing, completion dates and costs, or range of costs, of our drug development program, or of the successful development of any particular fixed-dose combination.

The potential success of any fixed-dose combination will depend on a number of factors, including the following:

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Our ability to achieve market acceptance of a fixed-dose combination of VASCEPA and a statin.

*The continued scale, scope and duration of business interruptions caused by the COVID-19 pandemic and related recovery efforts remain uncertain.

Despite recent improvements, the ongoing presence of COVID-19 has created significant volatility, uncertainty and disruption in healthcare, social, supply and economic infrastructures.

the duration, volatility and scope of the pandemic, including resurgences, and the efficacy of recovery efforts;

governmental, business and individuals’

actions taken in response to the pandemic;

the impact of the pandemic on economic and political activity and our supply chain;

the effect on patients, healthcare providers and business partners, including patients’

ability to access supplies of VASCEPA and the willingness of patients to visit doctors for non-urgent medical examination or to visit labs for blood tests to assess biomarkers such as lipid levels;

the impact that changes in patients’

and healthcare providers’

behavior and practices regarding face to face visits may have on our commercialization efforts, including whether virtual interactions will be as impactful as traditional, in-person interactions;

any further, prolonged or reinstated closures of our and our partners’

offices, operations and facilities impeding our ability to work together as a company and with our business and healthcare partners.

Risks Related to Our Reliance on Third Parties

Our supply of product for the commercial market and clinical trials is dependent upon relationships with third-party manufacturers and suppliers.

We have no in-house manufacturing capacity and rely on contract manufacturers for our clinical and commercial product supply.

We have no in-house manufacturing capacity and rely entirely on contract manufacturers for our clinical and commercial product supply.

We cannot provide assurance that we will successfully manufacture any product we may develop, either independently or under manufacturing arrangements, if any, with our third-party manufacturers.

Moreover, if our manufacturers should cease doing business with us or experience delays, shortages of supply or excessive demands on their capacity, we may not be able to obtain adequate quantities of product in a timely manner, or at all.

Moreover, if our manufacturers should cease doing business with us or experience delays, shortages of supply or excessive demands on their capacity, or if they insist on burdensome terms, such as excessive minimum supply commitments, we may not be able to obtain adequate quantities of product in a timely manner, at cost efficient levels or at all.

If we are not able to continue to operate our business relationships in a manner that is sufficiently profitable for us and our suppliers, certain members of our supply chain could compete with us through supply to competitors, such as generic drug companies, through breach of our agreements or otherwise.

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Any reliance on suppliers may involve several risks, including a potential inability to obtain critical materials and reduced control over production costs, delivery schedules, reliability and quality.

Any unanticipated disruption to future contract manufacture caused by problems at suppliers could delay

shipment of products, increase our cost of goods sold and/or result in lost sales.

If our suppliers were unable to supply us with adequate volumes of active pharmaceutical ingredient, API, (drug substance) or encapsulated bulk product (drug product), it would have a material adverse effect on our ability to continue to commercialize VASCEPA.

Any unanticipated disruption to future contract manufacture caused by problems at suppliers could delay shipment of products, increase our cost of goods sold and/or result in lost sales.

If our suppliers were unable to supply us with adequate volumes of API (drug substance) or encapsulated bulk product (drug product), it would have a material adverse effect on our ability to continue to commercialize VASCEPA.

We have contractual freedom to source the API for VASCEPA and to procure other services supporting our supply chain.

We have entered into supply agreements with multiple suppliers who also rely on other third-party suppliers to manufacture the API and other elements necessary for the sale of VASCEPA.

Our strategy in sourcing API and other components in our supply chain from multiple suppliers has been to expand manufacturing capacity, maintain competitive advantages, and mitigate the risk of reliance on any single supplier.

We continue to take steps to negotiate our contract supply agreements to align supply arrangements with current and future global market demand.

Expanding manufacturing capacity and qualifying such capacity is complex and subject to numerous regulations and other operational challenges.

We require supply capacity to support our direct and indirect commercialization of VASCEPA.

We are also committed to providing supply to our commercial partners and distributors in Canada, China, the Middle East and North Africa, and we anticipate potential additional supply requirements as we pursue commercial opportunities in other countries.

We are also committed to providing supply to our commercial partners and distributors in Australia and New Zealand, Canada, China, the Middle East and North Africa, and we anticipate potential additional supply requirements as we pursue commercial opportunities in other countries.

The resources of our suppliers vary and are limited;

costs associated with projected expansion and qualification can be significant, and lead-times for supply purchases and capacity expansion are long requiring certain supply related decisions and commitment to be made in advance, for example, prior to commercial launch in China and in various European countries.

Our aggregate capacity to produce API is dependent upon the continued qualification of our API suppliers and, depending on the ability of existing suppliers to meet our supply demands, potentially the qualifications of new suppliers.

costs associated with projected expansion and qualification can be significant, and lead-times for supply purchases and capacity expansion are long requiring certain supply related decisions and commitment to be made in advance of commercial launch, including in China and various European countries.

If no additional API supplier is approved by the U.S.

FDA as part of an sNDA, our API supply will be limited to the API we purchase from previously approved suppliers.

Similarly, the EMA has not initially approved use of each of our suppliers used for VASCEPA in the United States for VAZKEPA in the EU.

While we believe that we have sufficient supply of VAZKEPA to support our initial launch plans in Europe, our supply in Europe will be limited until additional suppliers are qualified which qualifications could be delayed by COVID-19 and our exposure to manufacturing issues with our approved suppliers for the EU.

For example, the EMA has not yet approved use of each of our suppliers used for VASCEPA in the United States for supply of VAZKEPA in the EU.

Further, there can be no guarantee that current suppliers and future suppliers with which we have contracted to encapsulate API will be continually qualified to manufacture the product to our specifications or that current and any future suppliers will have the manufacturing capacity to meet anticipated demand for VASCEPA.

If our third-party manufacturing capacity is not appropriately qualified and/or compliant with applicable regulatory requirements, we may not be able to supply sufficient quantities of VASCEPA to meet anticipated demand.

We cannot guarantee that we can contract with any future manufacturer on acceptable terms or that any such alternative supplier will not require capital investment from us in order for them to meet our requirements.

Alternatively, our purchase of supply may exceed actual demand for VASCEPA.

There can be no guarantee that current suppliers and future suppliers with which we have contracted to encapsulate API will be continually qualified to manufacture the product to our specifications or that current and any future suppliers will have the manufacturing capacity to meet anticipated demand for VASCEPA.

We may purchase too much or not enough supply to satisfy actual demand, which could have a material adverse effect on our financial results and financial condition.

Alternatively, our purchase of supply, or any minimum purchase requirements, may exceed actual demand for VASCEPA.

Certain of our agreements with our suppliers include minimum purchase obligations and limited exclusivity provisions.

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We may not purchase sufficient quantities of VASCEPA to meet actual demand or we may be required to purchase more supply than needed to meet actual demand.

In either case, such event could have a material adverse effect on our financial results and financial condition.

If our minimum purchase commitments exceed our supply needs for VASCEPA, we may have to renegotiate with partners in our supply chain who may not be incentivized to renegotiate terms that are favorable to us, or at all.

If we are unable to secure adequate levels of supply to meet demand, our financial condition could be negatively and materially impacted.

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Collectively, these dynamics negatively affect our profitability for the sale of VASCEPA and could increase over time further impacting our operating results.

Consolidation among these industry participants could increase the pressure from these market dynamics.

Consolidation among these industry participants could increase the pressure on us from these market dynamics.

The manufacture, packaging and distribution of pharmaceutical products such as VASCEPA are subject to U.S.

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There are comparable foreign requirements under ICH guidelines.

In addition, certain COVID-19 restrictions have affected Regulatory Agencies' ability to conduct facility inspections and may affect the timing of further approvals.

In addition, certain past COVID-19 restrictions have affected Regulatory Agencies' ability to conduct facility inspections and may affect the timing of further approvals.

This review may be costly and time consuming and could delay or prevent the launch of a product.

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This requirement is referred to as process validation.

Process validation includes stability testing, measurement of impurities and testing of other product specifications by validated test methods.

Process validation includes stability testing,

measurement of impurities and testing of other product specifications by validated test methods.

FDA does not consider the result of the process validation or required testing to be satisfactory, the commercial supply of VASCEPA may be delayed, or we may not be able to supply sufficient quantities of VASCEPA to meet anticipated demand.

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FDA or similar foreign regulatory bodies.

For example, since March 2020 when foreign and domestic inspections of facilities were largely placed on hold, the

FDA has been working to resume routine surveillance, bioresearch monitoring and pre-approval inspections on a prioritized basis.

In April 2021, the U.S.

FDA resumed inspections, but on a limited basis, and employed remote interactive evaluations, using risk management methods, to meet user fee commitments and goal dates.

Lasting impacts from travel restrictions and continued uncertainties continue to impact oversight operations both domestic and abroad and it is unclear when standard operational levels will resume.

FDA is continuing to complete mission-critical work, prioritize other higher-tiered inspectional needs (e.g., for-cause inspections), and carry out surveillance inspections using risk-based approaches for evaluating public health.

Since March 2020 when foreign and domestic inspections of facilities were largely placed on hold, the U.S.

FDA has been working to resume pre-pandemic levels of inspection activities, including routine surveillance, bioresearch monitoring and pre-approval inspections.

Should the U.S.

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FDA does not determine a remote interactive evaluation to be adequate, the agency has stated that it generally intends to issue, depending on the circumstances, a complete response letter or defer action on the application until an inspection can be completed.

*Our commercialization of VASCEPA outside the United States is substantially dependent on third parties and other circumstances outside our control.

We have expanded our VASCEPA commercialization activities outside of the United States through several contractual arrangements in territories including China, the Middle East, North Africa and Canada.

During the COVID-19 public health emergency, a number of companies announced receipt of complete response letters due to the FDA’s inability to complete required inspections for their applications.

Regulatory authorities outside the U.S.

may adopt similar restrictions or other policy measures in response to the ongoing COVID-19 pandemic and may experience delays in their regulatory activities.

We are currently, and may continue to be, substantially dependent on third parties for our international efforts, and we may not be successful in negotiating or establishing relationships with business partners to support and maintain control over our international activities.

We continue to assess other opportunities to develop VASCEPA commercialization outside of the United States through similar arrangements.

In February 2015, we entered into a Development, Commercialization and Supply Agreement, or the DCS Agreement, with Edding, related to the development and commercialization of VASCEPA in the China Territory.

Under the DCS Agreement, Edding is responsible for development and commercialization activities in the China Territory and associated expenses.

For example, Edding is responsible for development and commercialization activities in the China Territory and associated expenses under our development, commercialization and supply agreement with them.

Additionally, Edding is required to conduct clinical trials in the China Territory to secure regulatory approval in certain territories.

In December 2017, Edding commenced a pivotal Phase 3 clinical trial aimed to demonstrate that VASCEPA lowers triglyceride levels and otherwise has beneficial effects in Chinese patients with severe hypertriglyceridemia (TG >500 mg/dL), as we previously demonstrated with VASCEPA in the more diverse population studied in the MARINE study.

In November 2020, we announced statistically significant positive topline results from Edding’s Phase 3 clinical trial of VASCEPA.

On February 9, 2021, we announced that the regulatory review processes for approval of VASCEPA in Mainland China and Hong Kong have commenced.

The Chinese National Medical Products Administration, or NMPA, has accepted for review the new drug application for VASCEPA, submitted by Edding, based on the results from the Phase 3 clinical trial and the results from our prior studies of VASCEPA.

Edding has communicated that they still anticipate an approval could be achieved before year-end in China.

On February 23, 2022 the Hong Kong Department of Health completed their evaluation and approved the use of VASCEPA under the REDUCE-IT indication.

Even though such results are similar to the MARINE study, additional clinical development efforts may be necessary in this market to demonstrate the effectiveness of VASCEPA in reducing major adverse cardiovascular events in Chinese patients with persistent cardiovascular risk.

Any development and regulatory efforts in the China Territory may be negatively impacted if the coronavirus pandemic worsens, continues or spreads, and if resources by regulators and industry professionals continue to be diverted to address the prolonged coronavirus pandemic.

Edding has successfully undertaken clinical trials and approval initiatives under our arrangement with them, including the announcement of statistically significant positive topline results from Edding’s Phase 3 clinical trial of VASCEPA and has obtained approval for VASCEPA in Hong Kong under the REDUCE-IT indication with anticipated approval in Mainland China expected by midyear 2023.

However, Edding may be required to undertake clinical development efforts in these markets, or Edding may face challenges or be unsuccessful in pursuing commercial launch.

Further, any development and regulatory efforts in the China Territory may be negatively impacted if the coronavirus pandemic worsens, continues or spreads, and if resources by regulators and industry professionals continue to be diverted to address the prolonged coronavirus pandemic.

Any development and regulatory efforts in the China Territory may be negatively impacted by heightened political tension between China and the United States, including in connection with COVID-19 and other issues expressed between the countries regarding trade practices, tariffs and honoring intellectual property rights.

If Edding is not able to effectively develop and commercialize VASCEPA in the China Territory, we may not be able to generate revenue from the DCS Agreement resulting from the sale of VASCEPA in the China Territory.

In March 2016, we entered into an agreement with Biologix FZCo, or Biologix, to register and commercialize VASCEPA in several Middle Eastern and North African countries.

Under the terms of the distribution agreement, we granted to Biologix a non-exclusive license to use our trademarks in connection with the importation, distribution, promotion, marketing and sale of VASCEPA in the Middle East and North Africa territory.

Biologix was approved under the MARINE indication in the following countries:

Lebanon in March 2018, United Arab Emirates in July 2018, Qatar in December 2019, Bahrain in April 2021, Kuwait in December 2021 and Saudi Arabia in March 2022.

VASCEPA was approved under the REDUCE-IT indication in the following countries:

Qatar in April 2021, Lebanon in August 2021, United Arab Emirates in October 2021 and Bahrain in April 2022.

VASCEPA was launched in Lebanon and the United Arab Emirates in June 2018 and February 2019, respectively.

VASCEPA is under registration in additional countries in the Middle East and North Africa regions.

Commercialization across the Middle East and North Africa is subject to similar risks as in the China Territory, and has been negatively impacted by COVID-19 and the destabilized local economies in the region.

In September 2017, we entered into an agreement with HLS Therapeutics Inc., or HLS, to register, commercialize and distribute VASCEPA in Canada.

Under the agreement, HLS is responsible for regulatory and commercialization activities and associated costs.

We are responsible for providing assistance towards local filings, supplying finished product under negotiated supply terms, maintaining intellectual property, and continuing the development and funding of REDUCE-IT related activities.

In December 2019, VASCEPA was approved for use in Canada to reduce the risk of cardiovascular events in statin-treated patients with elevated triglycerides, who are at high risk of cardiovascular events due to established cardiovascular disease, or diabetes, and at least one other cardiovascular risk factor.

In January 2020, HLS obtained an extended regulatory exclusivity designation.

In February 2020, HLS launched VASCEPA in Canada, with strong initial uptake before the impact of COVID-19 pandemic.

In July 2020, Patented Medicine Prices Review Board confirmed VASCEPA price is compliant with current guidelines, and CADTH recommended reimbursement for

VASCEPA in Canada in secondary prevention population.

As of September 30, 2022, reimbursement coverage is approximately 70% of publicly covered lives and 95% for private coverage.

Public reimbursement is now available in Ontario, Quebec, Saskatchewan, New Brunswick Northwest Territories and for the Non-Insured Health Benefits program for the First Nations and Inuit people.

Coverage of patients with established cardiovascular disease represents a substantial portion of VASCEPA’s approved label in Canada.

However, if HLS is not able to effectively commercialize VASCEPA in Canada through effective pricing (initially and over time), reimbursement or otherwise we may not be able to generate revenue from the sale of VASCEPA in Canada.

Our efforts to launch and support commercialization of VAZKEPA on our own in Europe is a complex undertaking for a company that, other than our launch of VAZKEPA in Germany in September 2021 (where operations were subsequently discontinued) and the launch of VAZKEPA in the UK in October 2022, has not launched or otherwise commercialized a product in Europe and could be subject to significant risks of execution to our successful development and revenue generation of VAZKEPA in Europe.

While various of our suppliers have been inspected and we do not anticipate supply availability limiting our launch in Europe, COVID-19 has limited the ability of suppliers to be inspected and not all of our suppliers have completed all of the requirements of the European regulatory authorities.

We are party to arrangements with Biologix FZCo, or Biologix, to register and commercialize VASCEPA in several Middle Eastern and North African countries, with HLS Therapeutics Inc., or HLS, to register, commercialize and distribute VASCEPA in Canada and with CSL Seqirus, or CSL, to commercialize and distribute VASCEPA in Australia and New Zealand.

Although Biologix is currently actively commercializing VASCEPA in the United Arab Emirates and Lebanon, and HLS is currently commercializing VASCEPA in Canada, we are completely reliant on these third parties to secure approval and successfully commercialize the product in those markets, which markets can be complex and challenging.

Further, development and commercialization across the Middle East and North Africa is subject to similar risks as in the China Territory, and has been negatively impacted by COVID-19 and the destabilized local economies in the region.

If Edding, Biologix, HLS or CSL, or other third parties who we rely on for development and commercialization of VASCEPA, do not successfully carry out their contractual obligations or meet expected deadlines, our recourse and remedies against these parties is limited.

Our efforts to launch and support commercialization of VAZKEPA on our own in Europe is a complex undertaking for a company that, other than our launch of VAZKEPA in Germany in September 2021 (where operations were subsequently discontinued) and the launch of VAZKEPA in certain countries in the fourth quarter of 2022, including the UK in October 2022, has not launched or otherwise commercialized a product in Europe and could be subject to significant risks of execution to our successful development and revenue generation of VAZKEPA in Europe.

We have limited experience working with partners outside the United States to develop and market our products in non-U.S.

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jurisdictions in a timely manner may limit the commercial success of VASCEPA and our ability to grow our revenues.

*Our relationships with healthcare providers and physicians and third-party payors are subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose use to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

Our relationships with healthcare providers and physicians and third-party payors are subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

Healthcare providers, physicians and third-party payors in the United States and elsewhere play a primary role in the recommendation and prescription of pharmaceutical products.

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In particular, the promotion, sales and marketing of healthcare items and services, as well as a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices.

The applicable federal and state healthcare laws and regulations laws that may affect our ability to operate include, but are not limited to:

Anti-Kickback Statute, which prohibits, among other things, knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs.

Liability may be established without a person or entity having actual knowledge of the federal anti-kickback statute or specific intent to violate it.

In addition, the government may assert that a claim including items or services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the FCA.

Although there are a number of statutory exemptions and regulatory safe harbors protecting certain activities from prosecution, the exemptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases, or recommendations may be subject to scrutiny if they do not qualify for an exemption or safe harbor.

Our practices may not in all cases meet all of the criteria for safe harbor protection from anti-kickback liability.

Violations are subject to significant civil and criminal fines and penalties for each violation, plus up to three times the renumeration involved, imprisonment, and exclusion from government healthcare workers;

the federal civil and criminal false claims laws and civil monetary penalties laws, including the FCA, which prohibits, among other things, any person from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment of government funds, or knowingly making or using, or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly concealing, or knowingly and improperly avoiding, decreasing, or concealing an obligation to pay money to the federal government.

The FCA also permits a private individual acting as a “whistleblower”

to bring actions on behalf of the federal government alleging violations of the statute and to share in any monetary recovery.

Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “case”

the submission of false or fraudulent claims.

Recently, several pharmaceutical and other healthcare companies have been investigated or faced enforcement actions under the FCA for a variety of alleged improper marketing activities, including allegations that they caused false claims to be submitted because of the company’s marketing of the product for unapproved, and thus allegedly non-reimbursable, uses.

Federal enforcement agencies also have showed increased interest in pharmaceutical companies’

product and patient assistance programs, including reimbursement and co-pay support services, and a number of investigations into these programs have resulted in significant civil and criminal settlements.

A claim that includes items or services resulting from a violations of the U.S.

Anti-Kickback Statute constitutes a false or fraudulent claim under the FCA.

When an entity is determined to have violated

the FCA, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs.

Pharmaceutical and other healthcare companies also are subject to other federal false claims laws, including, among others, federal criminal healthcare fraud and false statement statutes that extend to non-government health benefit programs;

HIPAA, which, among other things, imposes criminal and civil liability for knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payor and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services;

HIPAA, and its implementing regulations, which impose, among other things, requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization.

The Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’

fees and costs associated with pursuing federal civil actions;

the federal Physician Payment Sunshine Act, being implemented as the Open Payments Program, which requires manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to direct or indirect payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors) and teaching hospitals, as well as ownership and investment interests held in the company by physicians and their immediate family members.

Effective January 2022, applicable manufacturers also are required to report information regarding payments and transfers of value provided to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives;

federal governmental price reporting laws, which require the calculation and reporting of complex pricing metrics in an accurate and timely manner to government programs;

federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers;

and other state or local laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers;

restrict the ability of manufacturers to offer co-pay support to patients for certain prescription drugs;

require drug manufacturers to report information related to clinical trials, or information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures;

and/or require identification or licensing of sales representatives;

and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally.

Activities subject to these laws also involve the improper use of information obtained in the course of patient recruitment for clinical trials.

Refer to “

Business - Government Regulation - Fraud and Abuse Laws and Data Regulation " for further details.

The distribution of pharmaceutical products is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products.

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Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource-consuming and can divert a company’s attention from the business.

For example, in June 2020, we received a CID from the DOJ informing us that the DOJ is investigating whether aspects of our promotional speaker programs and copayment waiver program during the period from January 1, 2015 to the present violated the U.S.

Anti-Kickback Statute and the FCA in relation to the sale and marketing of VASCEPA by us and our previous co-marketing partner, Kowa America.

Similarly, in March 2021, the FTC issued a CID to us in connection with the FTC’s investigation of whether we have engaged in, or is engaging in, anticompetitive practices or unfair methods of competition relating to VASCEPA.

The New York State attorney general similarly issued a subpoena to us regarding the same subject matter on which the FTC CID is focused.

The investigations require us to produce documents and answer written questions, or interrogatories, relevant to specified time periods.

We are cooperating with the government.

We cannot predict

when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

For example, the June 2020 CIDs from the DOJ informing us that the DOJ is investigating whether aspects of our promotional speaker programs and copayment waiver program violated the U.S.

Anti-Kickback Statute, and from the FCA relating to the sale and marketing of VASCEPA by us and our previous co-marketing partner, Kowa America, as well as the March 2021 CID from the FTC in connection with the FTC’s investigation of whether we have engaged in, or are engaging in, anticompetitive practices or unfair methods of competition relating to VASCEPA require us to produce documents and answer written questions, or interrogatories, relevant to specified time periods;

as does the subpoena from the New York State attorney general regarding the same subject matter on which the FTC CID is focused.

As noted, we are cooperating with the government, but we cannot predict when these investigations will be resolved, the outcome of the investigations or their potential impact on our business.

Such investigations can be lengthy, costly and could materially affect and disrupt our business.

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Prohibitions or restrictions on sales or withdrawal of future marketed products could materially affect business in an adverse way.

Although compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent inappropriate conduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.

Third party patient assistance programs that receive financial support from companies have become the subject of enhanced government and regulatory scrutiny.

Government enforcement agencies have shown increased interest in pharmaceutical companies' product and patient assistance programs, including reimbursement support services, and a number of investigations into these programs have resulted in significant civil and criminal settlements.

government has established guidelines that suggest that it is lawful for pharmaceutical manufacturers to make donations to charitable organizations who provide co-pay assistance to Medicare patients, provided that such organizations, among other things, are bona fide charities, are entirely independent of and not controlled by the manufacturer, provide aid to applicants on a first-come basis according to consistent financial criteria and do not link aid to use of a donor's product.

However, donations to patient assistance programs have received some negative publicity and have been the subject of multiple government enforcement actions, related to allegations regarding their use to promote branded pharmaceutical products over other less costly alternatives.

Specifically, in recent years there have been multiple settlements resulting out of government claims challenging the legality of their patient assistance programs under a variety of federal and state laws.

It is possible that we may make grants to independent charitable foundations that help financially needy patients with their premium, co-pay, and co-insurance obligations.

If we choose to do so, and if we or our vendors or donation recipients are deemed to fail to comply with relevant laws, regulations or evolving government guidance in the operation of these programs, we could be subject to damages, fines, penalties, or other criminal, civil, or administrative sanctions or enforcement actions.

We cannot ensure that our compliance controls, policies, and procedures will be sufficient to protect against acts of our employees, business partners, or vendors that may violate the laws or regulations of the jurisdictions in which we operate.

Regardless of whether we have complied with the law, a government investigation could impact our business practices, harm our reputation, divert the attention of management, increase our expenses, and reduce the availability of foundation support for our patients who need assistance.

Further, it is possible that changes in insurer policies regarding co-pay coupons and/or the introduction and enactment of new legislation or regulatory measures impacting patients using affected products could have a material adverse effect on our sales, business and financial condition.

For example, on December 31, 2020, CMS published a new rule, effective January 1, 2023, requiring manufacturers to ensure the full value of co-pay assistance is passed on to the patient or these dollars will count toward the Average Manufacturer Price and Best Price calculation of the drug.

On May 17, 2022, the U.S.

District Court for the District of Columbia granted the Pharmaceutical Research and Manufacturers of America's, or PhRMA, motion for summary judgment invalidating the accumulator adjustment rule.

Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the current U.S.

presidential administration may reverse or otherwise change these measures, both the current U.S.

presidential administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

We cannot predict how the implementation of and any further changes to this rule will affect our business.

It is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent inappropriate conduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.

In addition, with the approval and commercialization of any of our products outside the United States, we will also likely be subject to foreign equivalents of the healthcare laws mentioned above, among other foreign laws.

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Risks Related to Our Intellectual Property

We are dependent on patents, proprietary rights and confidentiality to protect the commercial value and potential of VASCEPA.

We are dependent on patents, proprietary rights and confidentiality obligations of our employees, agents, business partners and third parties to protect the commercial value and potential of VASCEPA.

Enforcing our patent rights is challenging and costly and, even if we are able to successfully enforce our patent rights, our issued patents may not prevent competitors from competing with VASCEPA.

Our success depends in part on our ability to obtain and maintain intellectual property protection for our drug candidates, technology and know-how, and to operate without infringing the proprietary rights of others.

While certain key patents related to our product based on the MARINE clinical study were determined to be invalid as obvious by a district court in the United States, and we are pursuing an appeal process, it remains the case that our ability to successfully implement our business plan and to protect our products with our intellectual property will depend in large part on our ability to:

obtain, defend and maintain patent protection and market exclusivity for our current and future products;

preserve any trade secrets relating to our current and future products;

acquire patented or patentable products and technologies;

operate without infringing the proprietary rights of third parties.

We have prosecuted, and are currently prosecuting, multiple patent applications to protect the intellectual property developed during the VASCEPA development program.

As of the date of this report, we had 127 patent applications in the United States that have been either issued or allowed and more than 30 additional patent applications are pending in the United States.

Such 126 allowed and issued applications include the following:

one issued U.S.

patent directed to a pharmaceutical composition of VASCEPA in a capsule that expires in 2030;

patents covering or related to the use of VASCEPA in either the MARINE or ANCHOR populations that have terms that expire in 2030 or later;

patents covering or related to the use of VASCEPA in the REDUCE-IT population with terms expiring in 2033 or later;

three additional U.S.

patents directed to a pharmaceutical composition comprised of free fatty acids with a term that expires in 2030;

five additional patents related to the use of a pharmaceutical composition comprised of free fatty acids to treat the ANCHOR patient population with a term that expires in 2030 or later;

two additional patents related to the use of a pharmaceutical composition comprised of free fatty acids to treat the MARINE patient population with a term that expires in 2030;

three additional patents related to the use of a pharmaceutical composition comprised of free fatty acids to treat the REDUCE-IT population expiring 2033;

four additional patents related to a pharmaceutical composition comprised of free fatty acids and uses thereof to treat both the MARINE and ANCHOR patient populations with a term that expires in 2030;

one additional patent related to the use of a pharmaceutical composition comprised of re-esterified EPA triglyceride to treat the REDUCE-IT population expiring 2033;

four additional patents related to a formulation of EPA/DHA and uses thereof with a term that expires in 2030;

two additional patents related to the use of VASCEPA to treat obesity with a term that expires in 2034;

one additional patent related to the use of VASCEPA to treat prostate cancer with a term that expires in 2037;

four additional patents covering a pharmaceutical composition comprised of EPA and a hydroxyl compound with a term that expires in 2034;

six additional patents covering a new combination therapy comprised of EPA and another drug.

A Notice of Allowance is issued after the USPTO makes a determination that a patent can be granted from an application.

A Notice of Allowance does not afford patent protection until the underlying patent is issued by the USPTO.

No assurance can be given that applications with issued notices of allowance will be issued as patents or that any of our pending patent applications will issue as patents.

No assurance can be given that, if and when issued, our patents will prevent competitors from competing with VASCEPA.

For example, we may choose to not assert all issued patents in patent litigation and patents or claims within patents may be determined to be invalid.

We are the owner of the above-listed patents.

We are also the exclusive licensee of certain patents owned by others covering products and products in development.

We are also pursuing patent applications related to VASCEPA in multiple jurisdictions outside the United States.

Geographies outside the United States in which VASCEPA is sold and under regulatory review are not subject to the U.S.

patent litigation and judgment.

No litigation involving potential generic versions of VASCEPA is pending outside the United States.

VASCEPA is currently available by prescription in Canada, Lebanon and the United Arab Emirates.

In Canada, VASCEPA has the benefit of data protection afforded through Health Canada (until the end of 2027), in addition to separate patent protection with expiration dates that could extend into 2039.

We are pursuing additional regulatory approvals for VASCEPA in Europe, China and the Middle East.

In China and the Middle East, we are pursuing such regulatory approvals and subsequent commercialization of VASCEPA with commercial partners.

The EC approval provides ten years of market protection in the EU.

Furthermore, patent protection in Europe includes:

One granted patent related to the use of a pharmaceutical composition comprised of 4g of 96% EPA ethyl ester to treat the REDUCE-IT population expiring 2033.

Pending patent applications in Europe, if granted, may have the potential to extend exclusivity into 2039.

We may be dependent in some cases upon third-party licensors to pursue filing, prosecution and maintenance of patent rights or applications owned or controlled by those parties, including, for example, under our collaboration with Mochida.

It is possible that third parties will obtain patents or other proprietary rights that might be necessary or useful to us.

In cases where third parties are first to invent a particular product or technology, or first to file after various provisions of the America Invents Act of 2011 went into effect on March 16, 2013, it is possible that those parties will obtain patents that will be sufficiently broad so as to prevent us from utilizing such technology or commercializing our current and future products.

Although we intend to make reasonable efforts to protect our current and future intellectual property rights and to ensure that any proprietary technology we acquire or develop does not infringe the rights of other parties, we may not be able to ascertain the existence of all potentially conflicting claims.

Therefore, there is a risk that third parties may make claims of infringement against our current or future products or technologies.

In addition, third parties may be able to obtain patents that prevent the sale of our current or future products or require us to obtain a license and pay significant fees or royalties in order to continue selling such products.

We may in the future discover the existence of products that infringe patents that we own or that have been licensed to us.

If we were to initiate legal proceedings against a third party to stop such an infringement, such proceedings could be costly and time consuming, regardless of the outcome.

No assurances can be given that we would prevail, and it is possible that, during such a proceeding, our patent rights could be held to be invalid, unenforceable or both.

Although we intend to protect our trade secrets and proprietary know-how through confidentiality agreements with our manufacturers, employees and consultants, we may not be able to prevent parties subject to such confidentiality agreements from breaching these agreements or third parties from independently developing or learning of our trade secrets.

We anticipate that competitors may from time to time oppose our efforts to obtain patent protection for new technologies or to submit patented technologies for regulatory approvals.

Competitors may seek to oppose our patent applications to delay the approval process or to challenge our granted patents, for example, by requesting a reexamination of our patent at the USPTO, or by filing an opposition in a foreign patent office, even if the opposition or challenge has little or no merit.

For example, one of our patents was revoked in an opposition proceeding in Europe due to a determination of improper claim amendments under a provision of law not applicable in the United States.

Such proceedings are generally highly technical, expensive, and time consuming, and there can be no assurance that such a challenge would not result in the narrowing or complete revocation of any patent of ours that was so challenged.

Our issued patents may not prevent competitors from competing with VASCEPA, even if we are successful in enforcing our patent rights.

We plan to vigorously defend our rights under issued patents.

For example, on November 30, 2020 we filed a patent infringement lawsuit against Hikma for making, selling, offering to sell and importing generic icosapent ethyl capsules in and into the United States in a manner that we allege has induced the infringement of patents covering the use of VASCEPA to reduce specified cardiovascular risk.

We plan to vigorously defend our rights under issued patents, however such defense activities can be costly to pursue and may not have the desired results.

On November 30, 2020 we filed a patent infringement lawsuit against Hikma for making, selling, offering to sell and importing generic icosapent ethyl capsules in and into the United States in a manner that we allege has induced the infringement of patents covering the use of VASCEPA to reduce specified CV risk.

On January 25, 2021, we expanded the scope of this patent infringement lawsuit to include a health care insurance provider, Health Net, LLC.

On January 4, 2022, the district court hearing the case granted Hikma's motion to dismiss.

On October 13, 2022, the district court granted final judgement on the aspect of the litigation relating to the Company and Hikma.

intends to appeal the decision of the district court now that it is permitted to do so and also intends to continue to vigorously pursue its ongoing litigation with Health Net, but cannot predict the outcome or the impact on its business.

On October 13, 2022, the district court granted final judgement and the Company is appealing (Fed.

23-1169 filed November 21, 2022) the decision of the district court but cannot predict the outcome or the impact on its business.

We entered into a settlement agreement with Health Net, LLC on December 26, 2022.

The Company will continue to consider its legal options against parties similarly situated to Health Net and Hikma and acting in concert with either by making or selling any drug product or component thereof covered by the subject patents, or inducing others to do the same.

The Company intends to vigorously enforce its intellectual property rights relating to VASCEPA, but cannot predict the outcome of these lawsuits or any subsequently filed lawsuits.

Patent litigation is a time-consuming and costly process.

There can be no assurance that we will be successful in enforcing this patent or that it will not be successfully challenged and invalidated.

There can be no assurance that we will be successful in enforcing any patent or that it will not be successfully challenged and invalidated.

Even if we are successful in enforcing this patent, the process could take years to reach conclusion.

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Patent litigation is costly and time consuming, and we may not have sufficient resources to bring these actions to a successful conclusion.

There can be no assurance that any of our pending patent applications relating to VASCEPA or its use will issue as patents.

We have filed and are prosecuting numerous families of patent applications in the United States and internationally with claims designed to protect the proprietary position of VASCEPA.

We have pending patent applications relating to VASCEPA and its use.

We have filed and are prosecuting numerous families of patent applications in the United States and internationally with claims designed to protect the proprietary position of VASCEPA/VAZKEPA.

For certain of these patent families, we have filed multiple patent applications.

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Several of our patent applications contain claims that are based upon what we believe are unexpected and favorable findings from our clinical trials.

If granted, one or more of the resulting granted patents from REDUCE-IT, for example, would expire in 2039, beyond the 2030 and 2033 expiration dates of currently issued REDUCE-IT patents.

However, no assurance can be given that any of our pending patent applications will be granted or, if they grant, that they will prevent competitors from competing with VASCEPA.

However, our pending patent applications may not be granted or, if they grant, that they will prevent competitors from competing with VASCEPA.

Securing patent protection for a product is a complex process involving many legal and factual questions.

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In January 2023, we disclosed our 2023 financial outlook.

Subsequent to that, including in connection with the announcement of our cost and organizational restructuring plan, we have made statements about expected cost reductions and expenditures.

Such outlook and estimates are based on estimates, assumptions and the judgment of management.

Because of the inherent nature of estimates, including during the uncertainty of our European launch and the impact from U.S.

generic competition, we have suspended providing net revenue guidance and there could be significant differences between our estimates and the actual amount of product demand.

generic competition, we have suspended providing net revenue guidance, as there could be significant differences between our estimates and the actual amount of product demand.

If we fail to realize or if we change or update any element of our publicly disclosed financial guidance as we have done in the past or other expectations about our business and initiative change, our stock price could decline in value.

*The loss of key personnel could have an adverse effect on our business, particularly in light of our recent announcement of management succession plan.

*The loss of key personnel could have an adverse effect on our business, particularly in light of recent senior management changes.

We are highly dependent upon the efforts of our senior management.

The loss of the services of one or more members of senior management could have a material adverse effect on us.

Given our rapidly expanding enterprise coupled with a streamlined management structure and sales force, the departure of any key person could have a significant impact and would be potentially disruptive to our business until such time as a suitable replacement is hired.

Given our rapidly expanding enterprise coupled with a streamlined management structure and sales force and the changes to our Board and the recently announced departure of our Chief Executive Officer, the departure of any key person could have a significant impact and would be potentially disruptive to our business until such time as a suitable replacement is hired.

Furthermore, because of the specialized nature of our business, as our business plan progresses, we will be highly dependent upon our ability to attract and retain qualified scientific, technical and key management personnel.

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The number and complexity of these threats continue to increase over time.

For example, in June 2019, a report published by security researchers claimed that a database belonging to one of our vendors containing information about individuals who use or have expressed interest in VASCEPA was accessible to unauthorized users.

Although we were informed that such breach did not include social security numbers or credit card information, we cannot guarantee that a more material breach will not occur in the future.

In June 2019, a report published by security researchers claimed that a database belonging to one of our vendors containing information about individuals who use or have expressed interest in VASCEPA was accessible to unauthorized users.

Although we were informed that such breach did not include social security numbers or credit card information, a more material breach could occur in the future.

If a material breach of our information technology systems or those of our vendors occurs, the market perception of the effectiveness of our security measures could be harmed and our reputation and credibility could be damaged.

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Our and our subsidiaries’

income tax returns are periodically examined by various tax authorities, including the Internal Revenue Service, or the IRS, and states.

income tax returns are periodically examined by various tax authorities, including the Internal Revenue Service, or the IRS, and state tax authorities.

For example, the IRS began an examination of our 2018 U.S.

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gross product sales.

Customers A, B, and C accounted for 26%, 36%, and 31%, respectively, of gross product sales for the nine months ended September 30, 2022, and represented 41%, 32%, and 22%, respectively, of the gross accounts receivable balance as of September 30, 2022.

Customers A, B, and C accounted for 27%, 37%, and 28%, respectively, of gross product sales for the nine months ended September 30, 2021, and represented 34%, 37%, and 21%, respectively, of the gross accounts receivable balance as of September 30, 2021.

Customers A, B, and C accounted for 29%, 38%, and 27%, respectively, of gross product sales for the three months ended March 31, 2023, and represented 36%, 40%, and 20%, respectively, of the gross accounts receivable balance as of March 31, 2023.

Customers A, B, and C accounted for 21%, 39%, and 31%, respectively, of gross product sales for the three months ended March 31, 2022, and represented 29%, 37%, and 28%, respectively, of the gross accounts receivable balance as of March 31, 2022.

We expect that we may have customer concentration risk as we enter additional countries.

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We have not yet reached sustained profitability.

For the fiscal year ended December 31, 2022 and 2020, we reported net losses of approximately $105.8 million and $18.0 million, respectively.

For the fiscal year ended December 31, 2021, we reported net income of approximately $7.7 million.

For the fiscal years ended December 31, 2020 and 2019, we reported net losses of approximately $18.0 million and $22.6 million, and we had an accumulated deficit as of December 31, 2021 of $1.4 billion.

For the three months ended September 30, 2022 and 2021, we reported losses of approximately $5.1 million and $13.2 million, respectively, and we had an accumulated deficit as of September 30, 2022 of $1.5 billion.

Substantially all of our operating losses resulted from costs incurred in

connection with our research and development programs, from general and administrative costs associated with our operations, and costs related to the commercialization of VASCEPA.

Additionally, as a result of our significant expenses relating to research and development and to commercialization, we expect to continue to incur significant operating losses for an indefinite period.

We had an accumulated deficit as of December 31, 2022 of $1.5 billion.

For the three months ended March 31, 2023 and 2022, we reported losses of approximately $16.5 million and $31.6 million, respectively, and we had an accumulated deficit as of March 31, 2023 of $1.5 billion.

Substantially all of our operating losses resulted from costs incurred in connection with our research and development programs, from general and administrative costs associated with our operations, and costs related to the commercialization of VASCEPA.

Additionally, as a result of our significant expenses relating to commercialization and research and development, we expect to continue to incur significant operating losses for an indefinite period.

Because of the numerous risks and uncertainties associated with developing and commercializing pharmaceutical products, we are unable to predict the magnitude of these future losses.

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deficit and working capital.

Although we began generating revenue from VASCEPA in January 2013, we may never be consistently profitable for a full year.

We may never generate sufficient revenue to achieve a steady state of profitability.

Our ability to become profitable on a sustained basis depends upon our ability to generate revenue.

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We may not achieve profitability on a sustained basis in the near term due to high costs associated with, for example, our expanded commercialization efforts in the United States and our expected commercialization efforts in Europe.

If we are unable to continue to generate robust product revenues, we will not become profitable on a sustained basis in the near term, if ever, and may be unable to continue operations without continued funding.

If we are unable to consistently generate robust product revenues, we will not become profitable on a sustained basis in the near term, if ever, and may be unable to continue operations without continued funding.

Our operating results are unpredictable and may fluctuate.

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We believe that our quarterly and annual results of operations may be affected by a variety of factors, including those risks and uncertainties described in this Part II, Item 1A and the following:

the recent and potential launches of additional generic versions of VASCEPA;

continued and prolonged disruption to our business, or delays in resuming normal business activities, or reinstating restrictions after protocols have been lifted, from the COVID-19 pandemic;

the recent and future potential launches of additional generic versions of VASCEPA;

the timing and ability of efforts outside the United States , to develop, register and commercialize VASCEPA in Europe, the China Territory, several Middle Eastern and North African countries, and Canada, for example, including obtaining necessary regulatory approvals, favorable pricing and establishing marketing channels;

the continuing evolution of the medical community’s and the public’s perception of the REDUCE-IT study results;

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commercial or development activities, including as a result of political instability, civil unrest, terrorism, pandemics or other natural disasters, such as the coronavirus pandemic;

the timing and ability of efforts outside the United States, to develop, register and commercialize VASCEPA in Europe, the China Territory, several Middle Eastern and North African countries, and Canada, for example, including obtaining necessary regulatory approvals, favorable pricing and establishing marketing channels;

additional developments regarding our intellectual property portfolio and regulatory exclusivity protections, if any;

outcomes of litigation and other legal proceedings;

continued and prolonged disruption to our business, or delays in resuming normal business activities, or reinstating restrictions after protocols have been lifted, from the COVID-19 pandemic;

our ongoing regulatory dialogue.

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We currently operate with limited resources.

We believe that our cash and cash equivalents balance of $240.5 million and short-term investment balance of $63.2 million as of September 30, 2022 will be sufficient to fund our projected operations for at least 12 months from the issuance date of our unaudited condensed consolidated financial statements included elsewhere in this Quarterly Report.

We believe that our cash and cash equivalents balance of $191.4 million and short-term investment balance of $113.0 million as of March 31, 2023 will be sufficient to fund our projected operations for at least 12 months from the issuance date of our unaudited condensed consolidated financial statements included elsewhere in this Quarterly Report.

We have based this estimate on assumptions that may prove to be wrong, and we could deplete our capital resources sooner than we expect or fail to achieve positive cash flow.

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If additional capital is required and we are unable to obtain additional capital on satisfactory terms, or at all, we may be forced to delay, limit or eliminate certain promotional activities.

We anticipate that quarterly net cash outflows in future periods will be variable as a result of the timing of certain items, including our purchases of API, VASCEPA promotional and educational activities, including launch activities in Europe and the impact from COVID-19 on our operations and those of our customers and any current or potential generic competition.

We anticipate that quarterly net cash outflows in future periods will be variable as a result of the timing of certain items, including our purchases of API and VASCEPA promotional and educational activities, including launch activities in Europe on our operations and those of our customers and any current or potential generic competition.

In order to fully realize the market potential of VASCEPA, we may need to enter into a new strategic collaboration or raise additional capital.

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the timing, amount and consistency of revenue generated from the commercial sale of VASCEPA;

the costs associated with commercializing VASCEPA in the United States and increased sales force sizing, and for commercializing VAZKEPA in Europe, including hiring experienced professionals, and for additional regulatory approvals internationally, if any, the cost and timing of securing commercial supply of VASCEPA and the timing of entering into any new strategic collaboration with others relating to the commercialization of VASCEPA, if at all, and the terms of any such collaboration;

the costs associated with commercializing VASCEPA in the United States and sales force sizing, and for commercializing VAZKEPA in Europe, including hiring experienced professionals, and for additional regulatory approvals internationally, if any, the cost and timing of securing commercial supply of VASCEPA and the timing of entering into any new strategic collaboration with others relating to the commercialization of VASCEPA, if at all, and the terms of any such collaboration;

continued costs associated with litigation and other legal proceedings and governmental inquiries;

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Any change in our assessment of the realizability or the timing for realizing deferred taxes could have a negative impact our future profitability.

Changes in tax laws (including in response to the COVID-19 pandemic) or tax rulings, or changes in interpretations of existing laws, could cause us to be subject to additional income-based taxes and non-income taxes (such as payroll, sales, use, value-added, digital tax, net worth, property, and goods and services taxes), which in turn could materially affect our financial position and results of operations.

Changes in tax laws or tax rulings, or changes in interpretations of existing laws, could cause us to be subject to additional income-based taxes and non-income taxes (such as payroll, sales, use, value-added, digital tax, net worth, property, and goods and services taxes), which in turn could materially affect our financial position and results of operations.

In particular, there have been a number of significant changes to the U.S.

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The effect of any such tax reform is uncertain.

As we continue to expand internationally, we will be subject to varied and complex tax regimes, and the tax laws of one jurisdiction may

impact our expansion to or operations in other jurisdictions.

As we continue to expand internationally, we will be subject to varied and complex tax regimes, and the tax laws of one jurisdiction may impact our expansion to or operations in other jurisdictions.

Additionally, new, changed, modified, or newly interpreted or applied tax laws could increase our partners’

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In addition, the market prices of the securities of many pharmaceutical and medical technology companies have been especially volatile in the past, and this trend is expected to continue in the future.

As of October 21, 2022, we had 403,828,955 common shares outstanding including 383,347,128 shares held as ADSs and 20,481,827 held as ordinary shares (which are not held in the form of ADSs).

As of April 30, 2023, we had 407,687,476 common shares outstanding including 387,307,491 shares held as ADSs and 20,379,985 held as ordinary shares (which are not held in the form of ADSs).

There is a risk that there may not be sufficient liquidity in the market to accommodate significant increases in selling activity or the sale of a large block of our securities.

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period-to-period variations in our results of operations.

Further, the effects of Brexit are uncertain and may have a negative effect on global economic conditions, financial markets and our business, which could reduce the price of our ADSs and common shares.

In particular, Brexit could lead to a period of considerable uncertainty in relation to the UK financial and banking markets, as well as on the regulatory process in Europe, which could cause the broader global financial markets to experience significant volatility.

Further, the long-term effects of the UK's departure from the EU, or Brexit, remain uncertain and may have a negative effect on global economic conditions, financial markets and our business, which could reduce the price of our ADSs and common shares.

In particular, ongoing uncertainty related to Brexit and the long-term relationship between the UK and the EU could lead to a period of disruption in the UK financial and banking markets, as well as on the regulatory process in Europe, which could cause the broader global financial markets to experience significant volatility.

Asset valuations, currency exchange rates and credit ratings may also be subject to increased market volatility due to the ongoing uncertainty.

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Actual or potential sales of our common shares by our employees, including members of our senior management team, pursuant to pre-arranged stock trading plans could cause our stock price to fall or prevent it from increasing for numerous reasons, and actual or potential sales by such persons could be viewed negatively by other investors.

In accordance with the guidelines specified under Rule 10b5-1 under the Exchange Act and our policies regarding stock transactions, a number of our directors and employees, including members of our senior management team, have adopted and may continue to adopt pre-arranged stock trading plans to sell a portion of our common stock.

Generally, sales under such plans by members of our senior management team and directors require public filings.

Actual or potential sales of our ADSs by such persons could cause the price of our ADSs to fall or prevent it from increasing for numerous reasons.

For example, a substantial amount of our ADSs becoming available (or being perceived to become available) for sale in the public market could cause the market price of our ADSs to fall or prevent it from increasing.

A substantial amount of our ADSs becoming available (or being perceived to become available) for sale in the public market could cause the market price of our ADSs to fall or prevent it from increasing.

Also, actual or potential sales by such persons could be viewed negatively by other investors.

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to obtain 100% control of us.

Accordingly, acceptances of 90% of our

outstanding ordinary shares/ADSs will likely be a condition in any takeover offer to acquire us, not 50% as is more common in tender offers for corporations organized under Delaware law.

Accordingly, acceptances of 90% of our outstanding ordinary shares/ADSs will likely be a condition in any takeover offer to acquire us, not 50% as is more common in tender offers for corporations organized under Delaware law.

By contrast, a scheme of arrangement, the successful completion of which would result in a bidder obtaining 100% control of us, requires the approval of a majority of shareholders voting at the meeting and representing 75% of the ordinary shares voting for approval.

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However, because our place of central management and control is currently outside of the United Kingdom, we are not subject to the Takeover Code.

As a result, our shareholders are not entitled to the benefit of certain takeover offer protections provided under the Takeover Code.

As a result, our shareholders are not entitled to the benefit of certain takeover offer

protections provided under the Takeover Code.

The following is a brief summary of some of the most important rules of the Takeover Code which, as noted, does not apply to us:

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courts predicated upon the civil liability provisions of the federal securities laws of the United States.

We have been advised by our English solicitors that there is doubt as to the enforceability in England in original actions, or in actions for enforcement of judgments of U.S.

We have been advised by our English solicitors that there is doubt as to the enforceability in England in original actions, or in actions for

enforcement of judgments of U.S.

courts, of civil liabilities to the extent predicated upon the federal securities laws of the United States.

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Legal, political and economic uncertainty surrounding the exit of the UK from the EU may be a source of instability in international markets, create significant currency fluctuations, adversely affect our operations in the UK and pose additional risks to our business, revenue, financial condition, and results of operations.

The continued uncertainty concerning the UK’s legal, political and economic relationship with the EU after Brexit may be a source of instability in the international markets, create significant currency fluctuations, and/or otherwise adversely affect trading agreements or similar cross-border co-operation arrangements whether economic, tax, fiscal, legal, regulatory or otherwise.

These developments, or the perception that any of them could occur, may have a significant adverse effect on global economic conditions and the stability of global financial markets, and could significantly reduce global market liquidity and limit the ability of key market participants to operate in certain financial markets.

In particular, it could also lead to a period of considerable uncertainty

in relation to the UK financial and banking markets, as well as on the regulatory process in Europe.

The UK left the EU on January 31, 2020, but remained in the EU’s customs union and single market for a transitional period that expired on December 31, 2020.

Although the UK entered into a trade and cooperation agreement with the EU, which was provisionally applicable since January 1, 2021 and formally applicable since May 1, 2021, the UK-EU TCA, that provides for, among other things, the free movement of goods between the United Kingdom and the EU, continued legal uncertainty and potentially divergent national laws and regulations in areas not specifically addressed in the UK-EU TCA may continue to affect trade and other interactions between the UK and the EU.

In addition, UK service suppliers no longer benefit from automatic access to the entire EU single market and free movement of goods is subject to increased bureaucracy.

The loss of these benefits could impact the attractiveness of the UK as a global business and financial center, which may have an adverse effect on the rate of economic growth in the UK and the EU.

On a greater macroeconomic level, ongoing uncertainty related to Brexit and the UK’s legal, political and economic relationship with the EU may be a source of instability in the international markets, create significant currency fluctuations, and/or otherwise adversely affect trading agreements or similar cross-border cooperation arrangements whether economic, tax, fiscal, legal, regulatory or otherwise.

These developments may have a significant adverse effect on global economic conditions and the stability of global financial markets, and could significantly reduce global market liquidity and limit the ability of key market participants to operate in certain financial markets.

In particular, it could also lead to a period of considerable uncertainty in relation to the UK financial and banking markets, as well as on the regulatory process in Europe.

Asset valuations, currency exchange rates and credit ratings may also be subject to increased market volatility.

If the UK and the EU are unable to implement acceptable agreements or if other EU member states pursue withdrawal, barrier-free access between the UK and other EU member states or among the European Economic Area, or EEA, overall could be diminished or eliminated.

The long-term effects of Brexit will depend on any agreements (or lack thereof) between the UK and the EU.

Such a withdrawal from the EU is unprecedented, and it is unclear how the UK’s access to the European single market for goods, capital, services and labor within the EU, or single market, and the wider commercial, legal and regulatory environment, will impact our current and future operations (including business activities conducted by third parties and contract manufacturers on our behalf) and clinical activities in the UK.

The long-term effects of Brexit are currently unknown and will depend on the evolution of any agreements (or lack thereof) that the UK makes to retain access to the EU markets.

Such a withdrawal from the EU is unprecedented, and it remains unclear how the UK’s access to the European single market for goods, capital, services and labor within the EU, or single market, and the wider commercial, legal and regulatory environment, will impact our long-term operations (including business activities conducted by third parties and contract manufacturers on our behalf) and clinical activities in the UK.

In addition to the foregoing, our UK operations support our current and future operations and clinical activities in other countries in the EU and EEA and these operations and clinical activities could be disrupted by the ongoing effects of Brexit.

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The impact of the terms of the recent trade deal between the UK and EU are uncertain.

Since the regulatory framework in the UK covering quality, safety and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales and distribution of pharmaceutical products is derived from EU directives and regulations, Brexit could materially impact the future regulatory regime with respect to the commercialization of our products in the UK.

Since the regulatory framework in the UK covering quality, safety and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales and distribution of

pharmaceutical products is derived from EU directives and regulations, Brexit could materially impact the future regulatory regime with respect to the commercialization of our products in the UK.

Any delay in commercializing our products in the UK and/or the EU could restrict our ability to generate revenue and achieve and sustain profitability.

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We may also have to scale back or further restructure our operations.

If we are unable to obtain additional funding on a timely basis, we may be required to curtail or terminate some or all of our research or development programs or our commercialization strategies.

If we are unable to obtain additional funding when needed , we may be required to curtail or terminate some or all of our research or development programs or our commercialization strategies.

Raising additional capital may cause dilution to our existing shareholders, restrict our operations or require us to relinquish rights.

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As a result of these risks, we may not be able to achieve the expected benefits of any such transaction or collaboration or deliver the value thereof to our shareholders.

If we are unsuccessful in consummating any such transaction or collaboration, we may be

required to reevaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.

If we are unsuccessful in consummating any such transaction or collaboration, we may be required to reevaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.

We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, including in Europe, and record inflation.

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Although, to date, our business has not been materially impacted by these global economic and geopolitical conditions, it is impossible to predict the extent to which our operations will be impacted in the short and long term, or the ways in which such instability could impact our business and results of operations.

The extent and duration of these market disruptions, whether as a result of the military conflict between Russia and Ukraine, geopolitical tensions, record inflation or otherwise, are impossible to predict, but could be substantial.

The extent and duration of these market disruptions, whether as a result

of the military conflict between Russia and Ukraine, geopolitical tensions, record inflation or otherwise, are impossible to predict, but could be substantial.

Any such disruptions may also magnify the impact of other risks described in this report.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 1. Legal Proceedings