−Removed: We are a commercial-stage biopharmaceutical company focused on discovering and developing innovative and life-changing treatments for patients with serious, challenging and under-addressed neurological, endocrine and psychiatric disorders.
−Removed: We specialize in targeting and interrupting disease-causing mechanisms involving the interconnected pathways of the nervous and endocrine systems.
−Removed: Currently, we are primarily focused on the commercialization of INGREZZA ® (valbenazine) in the United States, or U.S., our first U.S.
−Removed: Food and Drug Administration, or FDA, approved product.
−Removed: In April 2017, we received FDA approval of our first product, INGREZZA, for the treatment of adults with tardive dyskinesia, or TD.
−Removed: Shortly after receiving FDA approval, we began commercializing INGREZZA in the U.S.
−Removed: using a specialty sales force primarily focused on educating physicians who treat patients with TD, including psychiatrists and neurologists.
−Removed: In addition to our first marketed product, our collaboration partner AbbVie Inc., or AbbVie, received approval of ORILISSA ® (elagolix) for the management of moderate to severe endometriosis pain in women from the FDA in July 2018 and Health Canada in October 2018.
−Removed: We receive royalties at tiered percentage rates on any net sales of ORILISSA.
−Removed: Our late-stage pipeline includes opicapone as an adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in adult Parkinson's disease patients, elagolix for the treatment of heavy menstrual bleeding, or HMB, associated with uterine fibroids in women, valbenazine for the treatment of chorea in adult patients with Huntington’s disease, or HD, and NBIb-1817 (VY-AADC) for the treatment of advanced Parkinson’s disease patients with motor fluctuations that are refractory to medical management.
−Removed: Our product candidates for uterine fibroids and advanced Parkinson’s disease are partnered with AbbVie and Voyager Therapeutics, Inc., or Voyager, respectively.
−Removed: In the third quarter of 2019, the FDA accepted our new drug application, or NDA, for opicapone for the treatment of Parkinson’s disease with a Prescription Drug User Fee Act, or PDUFA, target action date of April 26, 2020.
−Removed: Also, in the third quarter of 2019, the FDA accepted AbbVie’s NDA for elagolix for the treatment of uterine fibroids with a PDUFA target action date in the second quarter of 2020.
−Removed: Our early-stage clinical pipeline includes crinecerfont (NBI-74788) for the treatment of congenital adrenal hyperplasia, or CAH, elagolix for the treatment of polycystic ovary syndrome, or PCOS, in women and a vesicular monoamine transporter 2, or VMAT2, inhibitor with potential use in the treatment of neurologic and psychiatric disorders.
−Removed: Our product candidate for PCOS is partnered with AbbVie.
−Removed: In December 2019, we entered into a license and collaboration agreement with Xenon Pharmaceuticals Inc, or Xenon, a clinical-stage biopharmaceutical company.
−Removed: Pursuant to the terms of the agreement, we acquired an exclusive license to NBI-921352 (XEN901), a clinical-stage candidate with potential in epilepsy.
−Removed: In January 2020, we announced a collaboration and optional licensing agreement with Idorsia Pharmaceuticals Ltd, or Idorsia, granting us an option to license ACT-709478, a potent, selective, orally active and brain penetrating T-type calcium channel blocker, in clinical development for the treatment of a rare pediatric epilepsy.
−Removed: The option also includes a research collaboration to discover, identify and develop additional novel T-type calcium channel blockers.
−Removed: Going forward, we expect to augment our product pipeline by acquiring, through license or otherwise, additional drug candidates for research and development, or R&D, and potential commercialization.
+Added: We are a neuroscience-focused, biopharmaceutical company dedicated to discovering, developing and delivering life-changing treatments for people with serious, challenging and under-addressed neurological, endocrine and psychiatric disorders.
+Added: Our diverse portfolio includes United States Food and Drug Administration, or FDA, approved treatments for tardive dyskinesia, Parkinson’s disease, endometriosis*, uterine fibroids* and clinical programs in multiple therapeutic areas.
+Added: For nearly three decades, we have specialized in targeting and interrupting disease-causing mechanisms involving the interconnected pathways of the nervous and endocrine systems.
+Added: (*in collaboration with AbbVie Inc.)
Product Pipeline
−Removed: The following table summarizes our approved products and our most advanced product candidates currently in clinical development and is followed by detailed descriptions of each program:
−Removed: INGREZZA (valbenazine) – VMAT2 Inhibitor
+Added: Exclusive and Partnered Commercial Products
+Added: The following table summarizes our exclusive and partnered commercial products and is followed by detailed descriptions of each product:
+Added: INGREZZA (valbenazine)
+Added: We launched INGREZZA in the U.S.
+Added: in May 2017, after receiving FDA approval for INGREZZA as the first FDA-approved drug for the treatment of tardive dyskinesia in April 2017.
+Added: INGREZZA provides a once-daily dosing treatment option for tardive dyskinesia and has two dosing options (40 mg and 80 mg capsules), with 40 mg taken for the first seven days of treatment and an option to take 40 mg or 80 mg thereafter, depending on the patient’s dosing needs.
+Added: In February 2021, Mitsubishi Tanabe Pharmaceutical Company, or MTPC, reported positive top-line results from the J-KINECT Phase III study, designed to evaluate the efficacy and safety of valbenazine in tardive dyskinesia.
+Added: Detailed results from this trial will be presented at a future medical conference.
+Added: With positive data in hand, a marketing authorization with the Ministry of Health and Welfare is planned for 2021 in Japan.
+Added: In addition, MTPC submitted filings for marketing authorizations in South Korea, Thailand, Singapore, Indonesia, and Malaysia in 2020.
+Added: Tardive dyskinesia is defined by hyperkinetic involuntary movements which arise after months or years of treatment with dopamine receptor blocking agents, such as antipsychotics used for treating schizophrenia, bipolar disorder and depression, and certain treatments for nausea, vomiting and gastric emptying in patients with gastroparesis.
+Added: While the prevalence rates of tardive dyskinesia can vary greatly in accordance with the population being studied, it is estimated that over 500 thousand individuals are affected by tardive dyskinesia in the U.S.
+Added: alone (Kantar Health).
+Added: INGREZZA net product sales totaled $993.1 million, $752.9 million and $409.6 million for 2020, 2019 and 2018, respectively, and represented the significant majority of our total net product sales for 2020 and all of our net product sales for 2019 and 2018.
+Added: ONGENTYS (opicapone)
+Added: We launched ONGENTYS in the U.S.
+Added: in September 2020, after receiving FDA approval for ONGENTYS as an adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in adult Parkinson's disease patients in April 2020.
+Added: We acquired the U.S.
+Added: and Canada rights to ONGENTYS from BIAL – Portela & Ca, S.A., or BIAL, in the first quarter of 2017.
+Added: ONGENTYS is a novel, once-daily, peripherally acting, highly selective Catechol-O-methyltransferase, or COMT, inhibitor utilized as an adjunct therapy to levodopa/carbidopa in patients with Parkinson’s disease experiencing motor fluctuations.
+Added: COMT inhibitors are utilized to prolong the duration of effect of levodopa, the primary treatment option for Parkinson’s disease patients, during periods of the day where the effects of levodopa wear off and motor symptoms worsen, also referred to as “off-time.” Parkinson’s disease is a chronic and progressive movement disorder that affects approximately 1 million individuals in the U.S.
+Added: ORILISSA (elagolix)
+Added: AbbVie Inc., or AbbVie, launched ORILISSA in the U.S.
+Added: and Canada in August and November 2018, respectively, after receiving FDA and Health Canada approval for ORILISSA for the management of moderate to severe endometriosis pain in women in July and October 2018, respectively.
+Added: Discovered and developed through Phase II clinical studies by us, we out-licensed the global rights to elagolix to AbbVie in 2010.
+Added: The World Endometriosis Research Foundation estimates that there are over 170 million women worldwide who suffer from endometriosis, including approximately 7.5 million women in the U.S.
+Added: ORIAHNN (elagolix, estradiol, and norethindrone acetate;
+Added: AbbVie launched ORIAHNN in the U.S.
+Added: in June 2020, after receiving FDA approval for ORIAHNN as the first FDA-approved non-surgical, oral medication option for the management of heavy menstrual bleeding associated with uterine fibroids in pre-menopausal women in May 2020.
+Added: We out-licensed the global rights to elagolix to AbbVie in 2010.
+Added: Uterine fibroids are benign hormonally responsive tumors that form in the wall of the uterus with a prevalence rate of at least 25% (American College of Obstetricians and Gynecologists) and are a leading indication for hysterectomy in the U.S., with approximately 250,000 hysterectomies performed each year related to uterine fibroids (Whiteman et al AJOG 2008, 198, e1).
+Added: Clinical Development Pipeline
+Added: The following table summarizes our clinical development pipeline and is followed by detailed descriptions of each program:
+Added: valbenazine – VMAT2 Inhibitor
VMAT2 is a protein concentrated in the human brain that is essential for the transmission of nerve impulses between neurons.
1 unchanged sentence
Specifically, dopamine enables neurotransmission among nerve cells that are involved in voluntary and involuntary motor control.
−Removed: Disease states such as TD, Tourette syndrome, Huntington’s chorea, schizophrenia, and tardive dystonia are characterized in part by a hyperdopaminergic state in the brain, and modulation of neuronal dopamine levels may provide symptomatic benefits for patients with these conditions, among others.
−Removed: INGREZZA as a treatment for tardive dyskinesia.
−Removed: TD is defined by hyperkinetic involuntary movements which arise after months or years of treatment with dopamine receptor blocking agents, e.g.
−Removed: antipsychotics used for treating schizophrenia, bipolar disorder, and depression, and Reglan ® (metoclopramide) for nausea and vomiting and gastric emptying in patients with gastroparesis.
−Removed: Features of TD may include grimacing, tongue protrusion, lip smacking, puckering and pursing of the lips, and rapid eye blinking.
−Removed: Rapid movements of the extremities may also occur.
−Removed: The impact on daily function and the quality of life for individuals suffering from TD can be substantial.
−Removed: While the prevalence rates of TD can vary greatly in accordance with the population being studied, it is estimated that approximately 500,000 individuals are affected by TD in the U.S.
−Removed: alone (Kantar Health).
−Removed: On April 11, 2017, INGREZZA became the first FDA-approved drug for the treatment of TD.
−Removed: INGREZZA provides a once-daily dosing treatment option for TD causing reversible reduction of dopamine release at the nerve terminal by selectively inhibiting the pre-synaptic VMAT2.
−Removed: In vitro, INGREZZA is a highly selective inhibitor of human VMAT2 showing little or no affinity for VMAT1, other receptors, such as dopamine D2 receptors, other transporters or ion channels.
−Removed: INGREZZA for TD has two dosing options (40 mg and 80 mg) with 40 mg taken for the first seven days of treatment with an option of 40 mg or 80 mg thereafter depending on a patient’s dosing needs.
−Removed: INGREZZA was generally well tolerated during our clinical trials with no apparent drug-drug interactions with the most common emergent adverse event being mild and transient somnolence.
−Removed: Valbenazine as an investigational treatment for chorea associated with Huntington disease .
+Added: Disease states such as tardive dyskinesia, Tourette syndrome, Huntington’s chorea, schizophrenia, and tardive dystonia are characterized in part by a hyperdopaminergic state in the brain, and modulation of neuronal dopamine levels may provide symptomatic benefits for patients with these conditions, among others.
+Added: We are currently conducting the KINECT-HD study, a Phase III, randomized, placebo-controlled, double-blind, multi-center Phase III clinical study to evaluate the efficacy, safety and tolerability of valbenazine for the treatment of chorea in 120 patients with Huntington’s disease, or HD, with Phase III top-line data expected in the fourth quarter of 2021.
HD is a hereditary progressive neurodegenerative disorder, in which neurons within the brain break down, resulting in motor, cognitive and psychiatric symptoms.
3 unchanged sentences
HD is estimated to affect approximately 30,000 adults in the U.S., with more than 200,000 at risk of inheriting the disease (NORD).
−Removed: We are currently conducting KINECT-HD, a multi-center randomized, double-blind, placebo-controlled Phase III study to evaluate the efficacy, safety and tolerability of valbenazine for the treatment of chorea in patients with HD.
−Removed: elagolix – GnRH Antagonist
−Removed: GnRH is the endogenous peptide that binds to the GnRH receptor and stimulates the secretion of the pituitary hormones that are responsible for sex steroid production and normal reproductive function.
−Removed: Researchers have found that chronic administration of GnRH
−Removed: agonists, after initial stimulation, reversibly shuts down this transmitter pathway and is clinically useful in treating hormone-dependent diseases such as endometriosis and uterine fibroids.
−Removed: Orally active, nonpeptide GnRH antagonists potentially offer several advantages over injectable GnRH peptide drugs, including rapid onset of hormone suppression without hormonal flare.
−Removed: Also, injection site reactions commonly observed in peptide depots are avoided and dosing can be rapidly discontinued if necessary – a clinical management option not available with long-acting depot injections.
−Removed: Additionally, by using GnRH antagonists, it may be possible to alter the level of pituitary GnRH suppression thereby titrating circulating hormone levels.
−Removed: In the second quarter of 2010, we entered into an exclusive worldwide collaboration with AbbVie to develop and commercialize GnRH compounds for women’s and men’s health indications.
−Removed: Under the terms of the agreement, AbbVie is responsible for all development, marketing and commercialization costs and has responsibility for all regulatory interactions with the FDA related to elagolix and other GnRH compounds covered by the collaboration.
−Removed: Following our entry into the collaboration, AbbVie undertook the development of elagolix in uterine fibroids.
−Removed: Endometriosis.
−Removed: Endometriosis is associated with a multitude of symptoms, some of the most common of which include pain related both to menstruation (dysmenorrhea) and sexual intercourse (dyspareunia) as well as chronic pelvic pain throughout the menstrual cycle, infertility, and menorrhagia, among many others.
−Removed: The wide range of symptoms associated with endometriosis serves to complicate and delay diagnosis due to the significant overlap of symptoms with the disease profiles of other conditions.
−Removed: The World Endometriosis Research Foundation estimates that there are over 170 million women worldwide who suffer from endometriosis, including approximately 7.5 million women in the U.S.
−Removed: We believe that the availability of an oral treatment lacking the side effect profile of the currently available peptide GnRH agonists may be a desirable alternative to current pharmaceutical therapies and ultimately encourage a significantly higher treatment rate.
−Removed: In the second and third quarter of 2018, respectively, AbbVie announced FDA and Health Canada approval of ORILISSA for the management of endometriosis with associated moderate to severe pain in women.
−Removed: AbbVie began commercialization of ORILISSA in the U.S.
−Removed: in the third quarter of 2018.
−Removed: Uterine Fibroids.
−Removed: Uterine fibroids are benign hormonally responsive tumors that form in the wall of the uterus.
−Removed: They are the most common solid tumor in women with a prevalence rate of at least 25% (American College of Obstetricians and Gynecologists).
−Removed: While many women do not have symptoms, depending on the size, location and number, uterine fibroids can cause symptoms such as:
−Removed: longer, more frequent or heavy menstrual bleeding, menstrual pain, vaginal bleeding at time other than menstruation, pain in the abdomen or lower back, pain during sex, difficulty urinating, frequent urination, constipation or rectal pain.
−Removed: Due to the severity of symptoms, treatment sometimes requires surgery, including the removal of the uterus.
−Removed: In fact, uterine fibroids is a leading indication for hysterectomy in the U.S., with approximately 250,000 hysterectomies performed each year related to uterine fibroids (Whiteman et al AJOG 2008, 198, e1).
−Removed: We believe that a safe and effective oral therapy would be a preferred treatment regimen rather than surgical intervention.
−Removed: In the third quarter of 2019, the FDA accepted AbbVie’s NDA for elagolix for the treatment of HMB associated with uterine fibroids in women with a PDUFA target action date in the second quarter of 2020.
−Removed: Polycystic Ovary Syndrome.
−Removed: PCOS is one of the most common hormonal disorders among women of reproductive age, affecting approximately 3.5 million women in the U.S.
−Removed: PCOS occurs when the ovaries or adrenal glands produce more male hormones (androgens) than normal.
−Removed: Women with PCOS experience irregular menstrual periods, infertility, pelvic pain, weight gain, acne and excess hair growth on the face, chest, stomach and thighs.
−Removed: There is no cure for PCOS, and treatment options are limited.
−Removed: If left untreated, PCOS can lead to certain cancers, diabetes and coronary artery disease.
−Removed: AbbVie initiated a Phase II study of elagolix in patients with polycystic ovary syndrome in mid-2019.
−Removed: The study is designed to evaluate whether there is a potential impact on disordered hormonal dynamics in women with PCOS.
−Removed: opicapone – Catechol-O-methyltransferase Inhibitor
−Removed: Catechol-O-methyltransferase, or COMT, inhibitors are utilized to prolong the duration of effect of levodopa, the primary treatment option for Parkinson’s disease patients.
−Removed: Administration of levodopa often results in adequate control of Parkinson’s symptoms, also referred to as “on-time,” however, there are periods of the day where the effects of levodopa wear off and motor symptoms worsen.
−Removed: These periods are considered “off-time.” Opicapone is a novel, once-daily, peripherally acting, highly selective COMT inhibitor utilized as adjunct therapy to levodopa/carbidopa in patients with Parkinson’s disease experiencing motor fluctuations.
−Removed: Opicapone works through decreasing the conversion rate of levodopa into 3-O-methyldopa, thereby reducing the off-time period in patients with Parkinson’s disease and extending the on-time period.
−Removed: In the first quarter of 2017, we entered into an exclusive license agreement with BIAL – Portela & Ca, S.A., or BIAL, for the development and commercialization of opicapone for the treatment of human diseases and conditions, including Parkinson’s disease, in the U.S.
−Removed: Under the terms of the agreement, we will be responsible for the development and commercialization of opicapone in the U.S.
−Removed: Parkinson’s Disease .
−Removed: Parkinson’s disease is a chronic and progressive movement disorder that affects approximately one million people in the U.S.
−Removed: The disease is characterized by a loss of neurons in the substantia nigra, the area of the brain where dopamine is produced.
−Removed: Dopamine production and synthesis is necessary for coordination and movement.
−Removed: As Parkinson’s disease progresses, dopamine production steadily decreases resulting in tremor, slowed movement (bradykinesia), impaired posture and balance, and speech and writing problems.
−Removed: There is no present cure for Parkinson’s disease and management consists of controlling the motor symptoms primarily through administration of levodopa therapies.
−Removed: While this improves the control of Parkinson’s disease symptoms,
−Removed: as the disease progresses the beneficial effects of levodopa begin to wear off, symptoms worsen, and patients experience motor fluctuations.
−Removed: These motor fluctuations are improved with the addition of a COMT inhibitor to levodopa.
−Removed: In the third quarter of 2016, BIAL announced the European Medicines Agency’s, or EMA’s, approval of ONGENTYS ® (opicapone) as an adjunct therapy to preparations of levodopa/DOPA decarboxylase inhibitors in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilized on those combinations.
−Removed: In the third quarter of 2019, the FDA accepted our NDA for opicapone as an adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in adult Parkinson's disease patients with a PDUFA target action date of April 26, 2020.
−Removed: FDA approval of opicapone for Parkinson’s disease would trigger a milestone payment of $20.0 million, payable by us to BIAL.
−Removed: crinecerfont (NBI-74788) – Corticotropin-Releasing Factor Receptor 1 Antagonist
−Removed: Corticotropin-releasing factor 1 , or CRF 1 , is a hypothalamic hormone released directly into the hypophyseal portal vasculature which acts on the CRF 1 receptor, a G protein-coupled receptor, or GPCR, in the anterior pituitary to stimulate the release of adrenocorticotropin hormone, or ACTH.
+Added: NBI-921352 (XEN901) – Nav1.6 Sodium Channel Inhibitor
+Added: NBI-921352 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed to treat pediatric patients with SCN8A-DEE and other potential indications, including adult focal epilepsy.
+Added: The safety, tolerability and pharmacokinetics of NBI-921352 have been evaluated in a randomized, double-blind, placebo-controlled Phase I study using a powder-in-capsule formulation of NBI-921352 in healthy adult subjects.
+Added: Xenon has developed a pediatric-specific, granule formulation of NBI-921352, and completed juvenile toxicology studies to support pediatric development activities.
+Added: In October 2020, the FDA requested additional non-clinical data to support the IND we submitted in August 2020 in support of a Phase II clinical study for NBI-921352 in patients with SCN8A-DEE.
+Added: Based on feedback received in January 2021, we plan to initiate a Phase II clinical study in adolescent patients (aged 12 years and older) with SCN8A-DEE in the third quarter of 2021, and the study protocol will be amended to include younger pediatric patients (aged 2-11 years) with SCN8A-DEE as soon as the FDA has reviewed and approved additional non-clinical information.
+Added: We are also advancing clinical plans to initiate a Phase II clinical study of NBI-921352 for the treatment of adult focal epilepsy in 2021.
+Added: In addition, in October 2020, we announced the FDA granted us Rare Pediatric Disease Designation for NBI-921352 for the treatment of SCN8A-DEE.
+Added: SCN8A-DEE is a rare, extremely severe, single-gene epilepsy caused by mutations in the SCN8A gene that activates Nav1.6, the most highly expressed sodium channel in the excitatory pathways of the central nervous system, or CNS.
+Added: Children born with SCN8A-DEE typically start experiencing seizures between birth and 18 months of age, and most have multiple seizures per day.
+Added: Other symptoms include learning difficulties, muscle spasms, low or high muscle tone, poor coordination, developmental delay, and features similar to autism.
+Added: An estimated 10% of people with SCN8A are reported to have experienced sudden unexpected death in epilepsy.
+Added: The prevalence of SCN8A-DEE is estimated to be 1% of all developmental and epileptic encephalopathies (Larsen et al, Neurology 2015, 84, 480).
+Added: As SCN8A mutations were discovered only recently (i.e., in 2012), the number of SCN8A-DEE cases is expected to increase as awareness of and access to genetic surveillance increases.
+Added: SCN8A-DEE is generally refractory to anti-epilepsy treatments.
+Added: We are developing NBI-921352 with Xenon Pharmaceuticals Inc., or Xenon, as part of a strategic collaboration announced in December 2019.
+Added: NBI-827104 (ACT-709478) – T-type Calcium Channel Blocker
+Added: We acquired the global rights to NBI-827104 from Idorsia Pharmaceuticals Ltd., or Idorsia, in May 2020.
+Added: NBI-827104 is a potent, selective, orally active and brain penetrating T-type calcium channel blocker, being developed for the treatment of a rare pediatric epilepsy and other potential indications, including essential tremor.
+Added: In November 2020, we initiated a Phase II clinical study for NBI-827104 in a rare pediatric epileptic encephalopathy known as Continuous Spike and Wave During Sleep, or CSWS.
+Added: CSWS typically impacts children initially between the ages of two and four years old and manifests itself via a variety of seizure types, including atypical absence seizures, generalized tonic-clonic seizures and focal seizures that usually occur during sleep.
+Added: In addition, children with CSWS often present with cognitive, behavioral and developmental regression or delay.
+Added: Due to the differentiated mechanism of action of this molecule, when compared to non-selective calcium channel inhibitors, treatment with NBI-827104 could lead to an enhanced benefit risk profile for patients with this rare pediatric form of epilepsy.
+Added: In parallel we are advancing clinical plans to initiate a Proof of Concept clinical study of NBI-827104 for the treatment of essential tremor in 2021.
+Added: Endocrinology
+Added: crinecerfont (NBI-74788) – CRF1 Antagonist
+Added: Crinecerfont is a potent, selective, orally active, corticotropin-releasing factor1, or CRF1, receptor antagonist as demonstrated in a range of in vitro and in vivo assays.
+Added: CRF1, is a hypothalamic hormone released directly into the hypophyseal portal vasculature which acts on the CRF1 receptor, a G protein-coupled receptor, or GPCR, in the anterior pituitary to stimulate the release of adrenocorticotropin hormone, or ACTH.
The primary role of ACTH is the stimulation of the synthesis and release of adrenal steroids, including cortisol.
1 unchanged sentence
This tight control loop is known as the hypothalamic-pituitary-adrenal axis.
−Removed: Blockade of CRF 1 receptors at the pituitary has been shown to decrease the release of ACTH and subsequently attenuate the production and release of adrenal steroids.
−Removed: Classic Congenital Adrenal Hyperplasia.
−Removed: Classic CAH is a group of autosomal recessive genetic disorders that affects approximately 20,000-30,000 people in the U.S.
−Removed: and results in an enzyme deficiency altering the production of adrenal steroids.
+Added: Blockade of CRF1 receptors at the pituitary has been shown to decrease the release of ACTH, which in turn decreases the production of adrenal steroids including androgens, and potentially the symptoms associated with classic CAH.
+Added: Lower ACTH levels would also reduce the amount of exogenous corticosteroid necessary for classic CAH patients to thrive avoiding the side-effects currently associated with excessive steroid therapy.
+Added: Classic CAH is a group of autosomal recessive genetic disorders that affects approximately 30 thousand people in the U.S.
+Added: and approximately 50 thousand people in the EU, and results in an enzyme deficiency altering the production of adrenal steroids.
Because of this deficiency, the adrenal glands have little to no cortisol biosynthesis resulting in a potentially life-threatening condition.
4 unchanged sentences
resulting in metabolic syndrome, bone loss, growth impairment, and Cushing’s syndrome as common and serious side effects.
−Removed: Crinecerfont is a potent, selective, orally active, CRF 1 receptor antagonist as demonstrated in a range of in vitro and in vivo assays.
−Removed: Blockade of CRF 1 receptors at the pituitary has been shown to decrease the release of ACTH, which in turn decreases the production of adrenal steroids including androgens, and potentially the symptoms associated with classic CAH.
−Removed: Lower ACTH levels would also reduce the amount of exogenous corticosteroid necessary for classic CAH patients to thrive avoiding the side-effects currently associated with excessive steroid therapy.
−Removed: We conducted a Phase I single ascending dose study of crinecerfont in healthy volunteers in 2017.
−Removed: Based on the positive results of the Phase I study, we initiated a Phase II clinical study of crinecerfont in adult patients with classic CAH, which was designed to be an open-label, pharmacokinetic/pharmacodynamic study assessing key pharmacodynamic biomarkers including ACTH, 17-hydroxyprogesterone (17-OHP), androgen, and cortisol levels collected the morning following bedtime dosing on Day 1 and Day 14.
−Removed: In the first quarter of 2019, positive interim results from the ongoing Phase II study demonstrated a reduction of at least 50% from baseline in 17-hydroxyprogesterone (17-OHP) and ACTH levels in more than 50% of CAH patients treated with crinecerfont for 14 days.
−Removed: Meaningful reductions were also observed in other biomarkers, including androstenedione.
−Removed: Crinecerfont was shown to be well tolerated with no serious adverse events reported to date.
−Removed: We plan to start a global registration study in mid-2020 for crinecerfont in adult patients with CAH.
−Removed: In the third quarter of 2019, we initiated an adaptive, Phase II proof-of-concept study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of crinecerfont in pediatric patients with classic CAH.
We have been granted orphan drug designation for crinecerfont in the treatment of classic CAH in the U.S.
−Removed: and the EU Orphan drug designation is granted by the FDA to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S.
−Removed: and provides sponsors with development and commercial incentives for such designated compounds and medicines.
−Removed: NBIb-1817 – AADC Gene Replacement Therapy
−Removed: NBIb-1817 is an investigational gene therapy designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located, bypassing the substantia nigra neurons and enabling the neurons of the putamen to produce the AADC enzyme to convert levodopa into dopamine.
−Removed: With this approach, NBIb-1817 has the potential to durably enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements by restoring motor function in patients and improving symptoms following a single administration.
−Removed: NBIb-1817 is currently being evaluated in the Phase II RESTORE-1 study in patients who have been diagnosed with Parkinson’s disease for at least four years, are not responding adequately to oral medications, and have at least three hours of OFF-time during the day, as measured by a validated self-reported patient diary.
−Removed: Based upon feedback received from the FDA, we plan to implement an amended protocol for the RESTORE-1 study by mid-2020.
−Removed: Further, we plan to start the RESTORE-II registration study in the second half of 2020.
−Removed: We are developing NBI b -1817 with Voyager as part of a strategic collaboration announced in January 2019.
−Removed: NBI-921352 – Nav1.6 Sodium Channel Inhibitor
−Removed: NBI-921352 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed to treat pediatric patients with SCN8A-DEE and other potential indications, including adult focal epilepsy.
−Removed: SCN8A-DEE is a rare, extremely severe, single-gene epilepsy caused by mutations in the SCN8A gene that activates Nav1.6, the most highly expressed sodium channel in the excitatory pathways of the central nervous system, or CNS.
−Removed: Children born with SCN8A-DEE typically start experiencing seizures between birth and 18 months of age, and most have multiple seizures per day.
−Removed: Other symptoms include learning difficulties, muscle spasms, low or high muscle tone, poor coordination, developmental delay, and features similar to autism.
−Removed: An estimated 10% of people with SCN8A are reported to have experienced sudden unexpected death in epilepsy.
−Removed: The prevalence of SCN8A-DEE is estimated to be 1% of all developmental and epileptic encephalopathies (Larsen et al, Neurology 2015, 84, 480).
−Removed: As SCN8A mutations were discovered only recently (i.e., in 2012), the number of SCN8A-DEE cases is expected to increase as awareness of and access to genetic surveillance increases.
−Removed: SCN8A-DEE is generally refractory to anti-epilepsy treatments.
−Removed: The safety, tolerability and pharmacokinetics of NBI-921352 have been evaluated in a randomized, double-blind, placebo-controlled Phase I study using a powder-in-capsule formulation of NBI-921352 in healthy adult subjects.
−Removed: Xenon has developed a pediatric-specific, granule formulation of NBI-921352, and completed juvenile toxicology studies to support pediatric development activities.
−Removed: We plan to file an investigational new drug application, or IND, in mid-2020 to initiate a Phase II clinical study for NBI-921352 in pediatric patients with SCN8A-DEE.
−Removed: We are developing NBI-921352 with Xenon as part of a strategic collaboration announced in December 2019.
−Removed: ACT-709478 – T-type Calcium Channel Blocker
−Removed: ACT-709478 is a potent, selective, orally active and brain penetrating T-type calcium channel blocker for potential use in certain forms of generalized epilepsy.
−Removed: In January 2020, we announced a collaboration and optional licensing agreement with Idorsia, granting us an option to license ACT-709478, in clinical development for the treatment of a rare pediatric epilepsy.
−Removed: The option also includes a research collaboration to discover, identify and develop additional novel T-type calcium channel blockers.
−Removed: New VMAT2 Inhibitor
−Removed: We have filed an IND and completed dosing in the single ascending dose and multiple ascending dose portion of a Phase I study designed to assess initial safety, tolerability, and pharmacokinetics of a novel, internally discovered VMAT2 inhibitor.
−Removed: This compound has the potential to be used in the treatment of several neurology and/or psychiatry disorders.
−Removed: Studies assessing the initial safety, tolerability, and pharmacokinetics of this compound are ongoing.
+Added: In June 2020, positive data from a completed Phase II, open-label, pharmacokinetic/pharmacodynamic clinical study of crinecerfont in adult patients with classic CAH, which assessed key pharmacodynamic biomarkers including ACTH, 17-hydroxyprogesterone (17-OHP), androgen and cortisol levels collected the morning following bedtime dosing on Day 1 and Day 14, demonstrated meaningful reductions in elevated ACTH and 17-hydroxyprogesterone (17-OHP) levels (by 54% to 75%) at all doses studied, together with a dose-related decrease in androstenedione (A4) levels, ranging from 21% to 64%.
+Added: At the highest dose of crinecerfont (100 mg twice daily), 75% of patients showed a response of at least 50% reduction from baseline for each of the three hormone markers at day 14.
+Added: Treatment with crinecerfont was well tolerated with a favorable safety profile with no related serious adverse events reported.
+Added: Adverse events reported in two or more participants included headache, upper respiratory tract infection, fatigue, contusion, insomnia and nausea.
+Added: In July 2020, we initiated the CAHtalyst study, a global registrational Phase III, randomized, double-blind, placebo-controlled clinical study to evaluate the safety and efficacy of crinecerfont in 165 adult patients with classic CAH, followed by an open-label treatment period.
+Added: In July 2019, we initiated a Phase IIa proof-of-concept, pharmacokinetic/pharmacodynamic clinical study to evaluate the safety and tolerability of crinecerfont in pediatric patients with classic CAH.
+Added: We plan to initiate a single global registrational Phase III clinical study for crinecerfont in pediatric patients with CAH in 2021.
+Added: elagolix – GnRH Antagonist
+Added: The gonadotropin-releasing hormone, or GnRH, is the endogenous peptide that binds to the GnRH receptor and stimulates the secretion of the pituitary hormones that are responsible for sex steroid production and normal reproductive function.
+Added: Researchers have found that chronic administration of GnRH agonists, after initial stimulation, reversibly shuts down this transmitter pathway and is clinically useful in treating hormone-dependent diseases such as Polycystic Ovary Syndrome , or PCOS.
+Added: AbbVie initiated a Phase II clinical study of elagolix in patients with PCOS in mid-2019.
+Added: The study is designed to evaluate whether there is a potential impact on disordered hormonal dynamics in women with PCOS.
+Added: We out-licensed the global rights to elagolix to AbbVie in 2010.
+Added: PCOS is one of the most common hormonal disorders among women of reproductive age, affecting approximately 3.5 million women in the U.S.
+Added: PCOS occurs when the ovaries or adrenal glands produce more male hormones (androgens) than normal.
+Added: Women with PCOS experience irregular menstrual periods, infertility, pelvic pain, weight gain, acne and excess hair growth on the face, chest, stomach and thighs.
+Added: There is no cure for PCOS, and treatment options are limited.
+Added: If left untreated, PCOS can lead to certain cancers, diabetes and coronary artery disease.
+Added: We acquired the global rights to develop and commercialize NBI-1065844 (TAK-831), NBI-1065845 (TAK-653) and NBI-1065846 (TAK-041) from Takeda Pharmaceutical Company Limited, or Takeda, in June 2020.
+Added: NBI-1065844 (TAK-831) – DAAO Inhibitor
+Added: NBI-1065844 is a potential first-in-class D-Amino Acid Oxidase, or DAAO, inhibitor that has completed multiple Phase I clinical studies and is currently in on-going Phase II clinical studies, including the Phase II INTERACT proof-of-concept clinical study in negative symptoms of schizophrenia, with Phase II top-line data expected in the first quarter of 2021.
+Added: According to the World Health Organization, or WHO, 20 million people across the globe are affected by schizophrenia.
+Added: In the U.S., the prevalence of schizophrenia is estimated to be approximately 0.6% of the population.
+Added: The negative symptoms associated with schizophrenia describe a lessening or absence of behaviors and functions related to motivation and interest, or verbal and emotional expression.
+Added: There are currently no approved treatment options in the U.S.
+Added: for patients with predominant negative symptoms of schizophrenia.
+Added: NBI-1065844 is currently designated as a royalty-bearing product for Takeda.
+Added: Takeda retains a one-time opt-in right for a 50:50 profit share arrangement upon achievement of a certain development event.
+Added: NBI-1065845 (TAK-653) – AMPA Potentiator
+Added: NBI-1065845 is a potential first-in-class Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid, or AMPA, potentiator with the potential to be developed for treatment-resistant depression.
+Added: NBI-1065845 has completed multiple Phase I clinical studies.
+Added: We plan to initiate a Phase II clinical study of NBI-1065845 in treatment-resistant depression in 2021.
+Added: According to the WHO, major depressive disorder, or MDD, is one of the leading causes of disability.
+Added: While there are a number of marketed treatments for MDD, approximately 1/3 of patients do not benefit from them.
+Added: There is a significant need to develop new therapies with improved, faster onset of efficacy that are well tolerated.
+Added: NBI-1065845 is currently designated as a 50:50 profit share product with Takeda.
+Added: Takeda retains a one-time opt-out right to convert the designation to a royalty-bearing product dependent on a certain development event.
+Added: NBI-1065846 (TAK-041) – G Protein-Coupled Receptor 139 Agonist
+Added: NBI-1065846 is a potential first-in-class G Protein-Coupled Receptor 139, or GPR139, agonist with the potential to be developed for the treatment of anhedonia in depression.
+Added: NBI-1065846 has completed multiple Phase I clinical studies.
+Added: We plan to initiate a Phase II clinical study of NBI-1065846 in anhedonia in 2021.
+Added: Anhedonia is a psychological condition characterized by the inability to experience pleasure.
+Added: In patients with depression, anhedonia often does not improve with current treatments and predicts lack of functional improvement.
+Added: NBI-1065846 is currently designated as a 50:50 profit share product with Takeda.
+Added: Takeda retains a one-time opt-out right to convert the designation to a royalty-bearing product dependent on a certain development event.
Research Programs
−Removed: Our R&D focus is on addressing diseases and disorders of the central nervous and endocrine systems, which include therapeutic categories ranging from hypothalamic-pituitary-adrenal disorders to stress-related disorders and neurological/neuropsychiatric diseases.
+Added: We invest in research and development in order to address diseases and disorders of the central nervous and endocrine systems, which include therapeutic categories ranging from hypothalamic-pituitary-adrenal disorders to stress-related disorders and neurological/neuropsychiatric diseases.
CNS and endocrinology drug therapies are among the largest therapeutic categories, accounting for over $110 billion in drug sales in the U.S.
alone according to IQVIA (2018).
−Removed: CNS and Neuroendocrine Disorders (Targeted by GPCRs, Solute Carrier Proteins, and Ion Channels)
−Removed: GPCRs are the largest known gene superfamily of the human genome.
−Removed: Greater than 30% of all marketed prescription drugs act on GPCRs;
−Removed: which makes this class of proteins historically the most successful therapeutic target family.
−Removed: However, only a small fraction of the GPCR gene superfamily has been exploited.
−Removed: Ion channels appear to be represented by approximately 400 genes in the human genome and are currently the targets for approximately 8% (MAbs.
−Removed: 2019 Feb-Mar;
−Removed: 265–296) of the current marketed drugs.
−Removed: We believe that next-generation therapies derived from targeting GPCRs and ion channels will be discovered through the understanding of the complex relationships of drug/receptor interactions and their subsequent impact on efficacy, downstream signaling networks and regulation.
−Removed: Our GPCR research platform integrates drug discovery research efforts with a suite of assays and assay systems and automated analytical techniques.
−Removed: This process, now also applied to solute carrier proteins and ion channels, provides an unbiased profile of pharmacological protein/ligand interactions coupled with in vivo efficacy using discrete animal models allowing for rapid discovery of initial leads and advancement into preclinical and clinical development.
−Removed: Importantly, this design cycle is not limited to GPCRs, solute carrier proteins, or ion channel targets, but can be utilized for other recently identified proteins that play a role in human disease where current treatments or therapies are either inadequate or nonexistent.
Business Strategy
−Removed: Our mission is to improve the lives of patients living with serious and under-addressed neurological and endocrine-related diseases and disorders.
+Added: Our mission is to improve the lives of patients living with serious and under-addressed neurological, neuro-endocrinology and psychiatry related diseases and disorders.
The following are the key elements of our business strategy:
Commercializing Our Product Portfolio.
−Removed: In April 2017, we received approval from the FDA for INGREZZA for the treatment of TD.
−Removed: We market INGREZZA for TD in the U.S.
−Removed: The commercial launch of INGREZZA occurred on May 1, 2017.
−Removed: We have built a
−Removed: specialty sales force in the U.S.
+Added: In April 2017, we received approval from the FDA for INGREZZA for the treatment of tardive dyskinesia.
+Added: In April 2020, we received FDA approval for ONGENTYS as an adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in adult Parkinson's disease patients.
+Added: We market INGREZZA and ONGENTYS in the U.S.
+Added: The commercial launch of INGREZZA occurred in May 2017 and ONGENTYS occurred in September 2020.
+Added: We have built a specialty sales force in the U.S.
of approximately 250 experienced sales professionals.
−Removed: This specialty sales force focuses on promotion to physicians who treat TD patients, primarily neurologists and psychiatrists.
+Added: This specialty sales force focuses on promotion to physicians, primarily psychiatrists and neurologists.
Our commercial team is comprised of experienced professionals in marketing, access and reimbursement, managed markets, market research, commercial operations, and sales force planning and management.
8 unchanged sentences
We seek to identify and validate new medicines on novel targets for internal development or collaboration.
−Removed: We believe the creativity and productivity of our discovery research group will continue to be a critical component for our continued success.
+Added: We believe the creativity and productivity of our discovery research group will continue to be a critical component for our ongoing success.
Acquiring Rights to Commercial Products, Drug Development Candidates and Technologies.
3 unchanged sentences
The following is a summary of our significant collaborations/alliances:
−Removed: In June 2010, we announced an exclusive worldwide collaboration with AbbVie to develop and commercialize GnRH Compounds for women’s and men’s health.
−Removed: Under the terms of the agreement, AbbVie is responsible for all development, marketing and commercialization costs.
−Removed: We are entitled to a percentage of worldwide sales of GnRH Compounds for the longer of ten years or the life of the related patent rights.
−Removed: AbbVie may terminate the collaboration at its discretion upon 180 days written notice to us.
−Removed: In February 2017, we entered into an exclusive license agreement with BIAL for the development and commercialization of opicapone for the treatment of human diseases and conditions, including Parkinson’s disease, in the U.S.
−Removed: Under the terms of the agreement, we are responsible for the management and cost of all opicapone development and commercialization activities in the U.S.
−Removed: BIAL will be entitled to a percentage of net sales (with a floor minimum) in exchange for the manufacture and supply of opicapone drug product.
−Removed: Either party may terminate the agreement earlier if the other party materially breaches the agreement and does not cure the breach within a specified notice period, or upon the other party’s insolvency.
−Removed: BIAL may terminate the agreement if we fail to use commercially reasonable efforts or fail to file an NDA for a licensed product by a specified date or under certain circumstances involving a change of control.
+Added: In June 2020, we entered into an exclusive license agreement with Takeda, which became effective in July 2020, to develop and commercialize certain compounds in Takeda’s early to mid-stage psychiatry pipeline.
+Added: Specifically, Takeda granted us an exclusive license to the following seven assets:
+Added: (i) NBI-1065844 (TAK-831) for schizophrenia, (ii) NBI-1065845 (TAK-653) for treatment-resistant depression, (iii) NBI-1065846 (TAK-041) for anhedonia (which together with the NBI-1065845 are referred to as the Phase II Ready Assets), and (iv) four non-clinical stage assets, or the Non-Clinical Assets.
+Added: NBI-1065844 is deemed a royalty-bearing product under the license agreement pursuant to which we will be responsible for all costs and expenses associated with the development, manufacture, and commercialization of such asset, subject to certain exceptions, and Takeda will be eligible to receive development and commercial milestones and royalties with respect to such asset, or a Royalty-Bearing Product, and Takeda will retain the right to opt-in to a profit sharing arrangement pursuant to which we and Takeda will equally share in the operating profits and losses related to such asset, subject to certain exceptions, in lieu of receiving milestones and royalties, or a Profit-Share Product.
+Added: Subject to specified conditions, Takeda may elect to exercise such opt-in right for NBI-1065844 before we initiate a Phase III clinical trial.
+Added: Each of the Phase II Ready Assets is deemed a Profit-Share Product and Takeda will retain the right to opt-out of the profit-sharing arrangement for such asset pursuant to which such asset would become a Royalty-Bearing Product.
+Added: Takeda may elect to exercise such opt-out rights with respect to a Phase II
+Added: Ready Asset immediately following the completion of the second Phase II clinical trial for such Phase II Ready Asset.
+Added: In addition, under certain circumstances related to the development and commercialization activities to be performed by us, Takeda may elect to opt-out of the profit-sharing arrangement for a Profit-Share Product before the initiation of a Phase III clinical trial for such product.
+Added: Each of the Non-Clinical Assets will be Royalty-Bearing Products pursuant to which we will be responsible for all costs and expenses associated with the development, manufacture, and commercialization of such assets, subject to certain exceptions.
+Added: Unless earlier terminated, the license agreement will continue on a licensed product-by-licensed product and country-by-country basis until the date on which, (i) for any Royalty-Bearing Product, the royalty term has expired in such country;
+Added: and (ii) for any Profit-Share Product, for so long as we continue to develop, manufacture, or commercialize such licensed product.
+Added: We may terminate the license agreement for convenience in its entirety or in one or more (but not all) of the United States, Japan, the European Union, and the United Kingdom, or the Major Markets, on 6 months’ written notice to Takeda (i) with respect to all licensed products prior to the first commercial sale of the first licensed product for which first commercial sale occurs, or (ii) with respect to all licensed products in one or more given target classes, as defined in the agreement, prior to the first commercial sale of the first licensed product in such target class(es) for which first commercial sale occurs.
+Added: We may terminate the license agreement for convenience in its entirety or in one or more (but not all) of the Major Markets on 12 months’ written notice to Takeda (i) with respect to all licensed products following the first commercial sale of the first licensed product for which first commercial sale occurs, or (ii) with respect to all licensed products in one or more given target classes following the first commercial sale of the first licensed product in such target class(es) for which first commercial sale.
+Added: Takeda may terminate the license agreement, subject to specified conditions, (i) if we challenge the validity or enforceability of certain Takeda intellectual property rights or (ii) on a target class-by-target class basis, in the event that we do not conduct any material development or commercialization activities with respect to any licensed product within such target class for a specified continuous period.
+Added: Subject to a cure period, either party may terminate the license agreement in the event of any material breach, solely with respect to the target class of a licensed product to which such material breach relates, or in its entirety in the event of any material breach that relates to all licensed products.
+Added: We acquired the global rights to NBI-827104 from Idorsia in May 2020.
+Added: NBI-827104 is a potent, selective, orally active and brain penetrating T-type calcium channel blocker, being developed for the treatment of a rare pediatric epilepsy and other potential indications, including essential tremor.
+Added: The agreement also included a research collaboration to discover and identify additional novel T-type calcium channel blockers as development candidates.
+Added: Under the terms of the agreement, we are responsible for all manufacturing, development and commercialization costs of any collaboration product.
+Added: We may terminate the collaboration and licensing agreement, in its entirety or with respect to a particular compound or development candidate, by providing 90 days’ written notice to Idorsia.
+Added: Further, in the event a party commits a material breach and fails to cure such material breach within 90 days after receiving written notice thereof, the non-breaching party may terminate the agreement in its entirety immediately upon written notice to the breaching party.
+Added: In December 2019, we entered into a license and collaboration agreement with Xenon to identify, research, and develop sodium channel inhibitors, including clinical candidate NBI-921352 and three preclinical candidates, which compounds we will have the exclusive right to further develop and commercialize under the terms and conditions set forth in the agreement.
+Added: We will be solely responsible, at our sole cost and expense, for all development and manufacturing of the compounds and any pharmaceutical product that contains a compound, subject to Xenon’s right to elect to co-fund the development of one product in a major indication and thus receive a mid-single digit percentage increase in royalties owed on the net sales of such product in the U.S.
+Added: If Xenon exercises such option, the parties will share equally all reasonable and documented costs and expenses incurred in connection with the development of such product in the applicable indication, except costs and expenses that are solely related to the development of such product for regulatory approval outside the U.S.
+Added: Unless earlier terminated, the term of the license and collaboration agreement will continue on a product-by-product and country-by-country basis until the expiration of the royalty term for such product in such country.
+Added: Upon the expiration of the royalty term for a particular product and country, the exclusive license granted by Xenon to us with
+Added: respect to such product and country will become fully paid, royalty free, perpetual, and irrevocable.
+Added: We may terminate the license and collaboration agreement by providing at least 90 days’ written notice, provided that such unilateral termination will not be effective for certain products until we have used commercially reasonable efforts to complete certain specified clinical studies.
+Added: Either party may terminate the agreement in the event of a material breach in whole or in part, subject to specified conditions.
We entered into a collaboration and license agreement with Voyager, a clinical-stage gene therapy company, which became effective in March 2019.
4 unchanged sentences
Further, upon the occurrence of a specified event for each program, we will assume responsibility for the development, manufacturing, and commercialization activities of such program.
−Removed: In June 2019, we entered into an amendment to the collaboration and license agreement with Voyager.
−Removed: Under the terms of the amendment, we obtained rights outside the U.S.
−Removed: to the Friedreich’s ataxia program in connection with the early return of those rights to Voyager pursuant to a restructuring of Voyager’s gene therapy relationship with Sanofi Genzyme.
−Removed: We may terminate the collaboration and license agreement with Voyager upon 180 days written notice to Voyager prior to the first commercial sale of any collaboration product or upon 1 year after the date of notice if such notice is provided after the first commercial sale of any collaboration product.
+Added: On February 2, 2021, we notified Voyager of our termination of the NBIb-1817 for Parkinson’s disease program.
+Added: The effective date of this termination will be August 2, 2021.
+Added: The termination does not apply to any other development program other than NBIb-1817 for Parkinson’s disease, and our collaboration and license agreement with Voyager will otherwise continue in effect.
+Added: With respect to the other programs, we may terminate the collaboration and license agreement with Voyager upon 180 days written notice to Voyager prior to the first commercial sale of any collaboration product or upon 1 year after the date of notice if such notice is provided after the first commercial sale of any collaboration product.
Unless terminated earlier, the agreement will continue in effect until the expiration of the last to expire royalty term with respect to any collaboration product or the last expiration or termination of any exercised co-development and co-commercialization rights by Voyager as provided for in the agreement.
−Removed: In December 2019, we entered into a license and collaboration agreement with Xenon, a clinical-stage biopharmaceutical company.
−Removed: Pursuant to the terms of the agreement, we acquired an exclusive license to NBI-921352, a clinical stage selective Nav1.6 sodium channel inhibitor with potential in SCN8A-DEE and other forms of epilepsy.
−Removed: We also acquired an exclusive license to pre-clinical compounds for development, including selective Nav1.6 and dual Nav1.2/1.6 inhibitors.
−Removed: The agreement also includes a multi-year research collaboration to discover, identify and develop additional Nav1.6 and Nav1.2/1.6 inhibitors.
−Removed: Unless earlier terminated, the term of the license and collaboration agreement will continue on a product-by-product and country-by-country basis until expiration of the royalty term for such product in such country.
−Removed: Upon the expiration of the royalty term for a particular product and country, the exclusive license granted by Xenon to us with respect to such product and country will become fully paid, royalty free, perpetual and irrevocable.
−Removed: We may terminate the license and collaboration agreement by providing at least 90 days’ written notice, provided that such unilateral termination will not be effective for certain products until we have used commercially reasonable efforts
−Removed: to complete certain specified clinical studies .
−Removed: Either party may terminate the agreement in the event of a material breach in whole or in part, subject to specified conditions.
−Removed: Mitsubishi Tanabe Pharma Corporation.
−Removed: In March 2015, we entered into a collaboration and license agreement with Mitsubishi Tanabe Pharma Corporation , or MTPC, for the development and commercialization of INGREZZA for movement disorders in Japan and other select Asian markets.
+Added: We acquired the U.S.
+Added: and Canada rights to ONGENTYS from BIAL in the first quarter of 2017.
+Added: We launched ONGENTYS in the U.S.
+Added: in September 2020, after receiving FDA approval for ONGENTYS as an adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in adult Parkinson's disease patients in April 2020.
+Added: Under the terms of the agreement, we are responsible for the commercialization of ONGENTYS in the U.S.
+Added: Further, we rely on BIAL for the commercial supply of ONGENTYS.
+Added: Upon our written request prior to the estimated expiration of the term of a licensed product, the parties shall negotiate a good faith continuation of BIAL’s supply of such licensed product after the term.
+Added: After the term, and if BIAL is not supplying a certain licensed product, we shall pay BIAL a trademark royalty based on the net sales of such licensed product.
+Added: Upon commercialization of ONGENTYS, we determined certain annual sales forecasts.
+Added: In the event we fail to meet the minimum sales requirements for a particular year, we would be obligated to pay BIAL an amount equal to the difference between the actual net sales and minimum sales requirements for such year.
+Added: Unless earlier terminated, the agreement will continue on a licensed product-by-product and country-by-country basis until a generic product in respect of such licensed product under the agreement is sold in a country and sales of such generic product are greater than a specified percentage of total sales of such licensed product in such country.
+Added: Either party may terminate the agreement if the other party materially breaches the agreement and does not cure the breach within a specified notice period, or upon the other party’s insolvency.
+Added: BIAL may terminate the agreement if we fail to use commercially reasonable efforts to submit a new drug application, or NDA, for a licensed product by a specified date, in the event we fail to meet the minimum sales requirements for any two years, or under certain circumstances involving a change of control of Neurocrine Biosciences.
+Added: Under certain circumstances where BIAL elects to terminate the agreement in connection with a change of control of Neurocrine Biosciences, BIAL would be obligated to pay us a termination fee.
+Added: We may terminate the agreement at any time for any reason upon nine months’ written notice to BIAL.
+Added: In March 2015, we entered into a collaboration and license agreement with MTPC for the development and commercialization of INGREZZA for movement disorders in Japan and other select Asian markets.
Under the terms of the agreement, MTPC is responsible for all development, marketing and commercialization costs in Japan and other select Asian markets, with the exception of a single Huntington’s chorea study to be performed by us.
−Removed: We will be entitled to a percentage of sales of INGREZZA in Japan and other select Asian markets for the longer of ten years or the life of the related patent rights.
+Added: be entitled to a percentage of sales of INGREZZA in Japan and other select Asian markets for the longer of ten years or the life of the related patent rights.
MTPC may terminate the agreement at its discretion upon 180 days’ written notice to us.
In such event, all INGREZZA product rights for Japan and other select Asian markets would revert to us.
−Removed: In November 2019, we initiated the KINECT-HD study, a placebo-controlled Phase III study of valbenazine in adult Huntington’s disease patients with chorea.
−Removed: In January 2020, we announced a collaboration and optional licensing agreement with Idorsia, granting us an option to license ACT-709478, a potent, selective, orally active and brain penetrating T-type calcium channel blocker, in clinical development for the treatment of a rare pediatric epilepsy.
−Removed: The option also includes a research collaboration to discover, identify and develop additional novel T-type calcium channel blockers.
+Added: In June 2010, we entered into an exclusive worldwide collaboration with AbbVie to develop and commercialize elagolix and all next-generation GnRH antagonists, or collectively the GnRH Compounds, for women’s and men’s health.
+Added: AbbVie received approval of ORILISSA for the management of moderate to severe endometriosis pain in women from the FDA in July 2018 and Health Canada in October 2018.
+Added: In May 2020, AbbVie received approval from the FDA for ORIAHNN for the management of heavy menstrual bleeding associated with uterine fibroids in pre-menopausal women.
+Added: Under the terms of the agreement, AbbVie is responsible for all third-party development, marketing, and commercialization costs.
+Added: We are entitled to a percentage of worldwide sales of GnRH Compounds for the longer of ten years or the life of the related patent rights.
+Added: AbbVie may terminate the collaboration at its discretion upon 180 days’ written notice to us.
Intellectual Property
7 unchanged sentences
patents and certain patents covering our early-stage product candidates):
−Removed: INGREZZA, our highly selective VMAT2 inhibitor for the treatment of TD, is covered by three issued U.S.
−Removed: patents that are listed in the FDA’s Orange Book:
−Removed: 8,039,627, which expires in 2029 (not including a potential patent term extension of up to an additional two years), U.S.
−Removed: 8,357,697, which expires in 2027, and U.S.
−Removed: 10,065,952, which expires in 2036.
−Removed: ORILISSA, our small molecule GnRH antagonist for the treatment of endometriosis, is covered by six issued U.S.
−Removed: patents that are listed in the FDA’s Orange Book:
−Removed: 6,872,728, 7,179,815 and 7,462,625 expire in 2021 (not including potential patent term extensions of up to an additional five years) while U.S.
−Removed: 7,056,927, 7,176,211 and 7,419,983 expire in 2024 (not including potential patent term extensions of up to an additional five years).
−Removed: Opicapone, a highly selective COMT inhibitor for Parkinson’s disease, is covered by U.S.
−Removed: 8,168,793, among others, which expires in 2029 (not including a potential patent term extension of up to an additional five years).
+Added: • INGREZZA, our highly selective VMAT2 inhibitor for the treatment of tardive dyskinesia, is covered by eight issued U.S.
+Added: patents that are listed in the FDA’s Orange Book and are set to expire between 2027 and 2037.
+Added: There is also a potential patent term extension of up to an additional two years for U.S.
+Added: 8,039,627, which is currently set to expire in 2029 and is the earliest patent covering valbenazine, the active pharmaceutical ingredient contained in INGREZZA.
+Added: In Japan and certain other East Asian markets, we are actively pursuing most of the patents corresponding to those listed in the FDA’s Orange Book entry for INGREZZA.
+Added: • ONGENTYS, a highly selective COMT inhibitor for Parkinson’s disease, is covered by nine issued U.S.
+Added: patents that are listed in the FDA’s Orange Book and set to expire between 2026 to 2035 (not including a potential patent term extension of up to an additional four years for one of these patents).
+Added: • ORILISSA, our small molecule GnRH antagonist for the treatment of endometriosis pain, is covered by eight issued U.S.
+Added: patents that are listed in the FDA’s Orange Book and are set to expire between 2021 to 2036 (not including a potential patent term extension of up to an additional five years for one of the patents currently set to expire either in 2021 or 2024).
+Added: • ORIAHNN, containing our small molecule GnRH antagonist for the treatment of menstrual bleeding associated with uterine fibroids, is covered by six issued U.S.
+Added: patents that are listed in the FDA’s Orange Book and are set to expire between 2021 to 2024 (not including a potential patent term extension of up to an additional five years for one of the patents).
+Added: • Valbenazine, our highly selective VMAT2 inhibitor under further clinical development for the treatment of chorea in Huntington’s disease, is covered by at least six of the issued U.S.
+Added: patents that are listed in the FDA’s Orange Book entry for INGREZZA and are set to expire between 2027 and 2036 .
+Added: There is also a potential patent term extension of up to an additional two years for U.S.
+Added: 8,039,627, which is currently set to expire in 2029.
• Crinecerfont, our CRF1 antagonist for the treatment of CAH, is covered by U.S.
−Removed: 6,586,456, which expires in 2020, and U.S.
−Removed: 8,420,679, which expires in 2022 (both patents are expected to expire prior to marketing approval for crinecerfont and thus be ineligible for patent term extension).
−Removed: NBIb-1817, our AADC gene therapy for the treatment of Parkinson’s disease, is covered by patent applications that have an earliest priority date in 2017.
−Removed: The terms of any patents that may issue from these patent applications should be capable of continuing until 2038 in most jurisdictions without taking into account any patent term adjustment or extension regime.
−Removed: NBI-921352, an inhibitor of the Nav1.6 voltage-gated sodium channel for the treatment of epilepsy, is covered by U.S.
−Removed: US 10,246,453 which expires in 2037 (not including a potential patent term extension of up to an additional five years).
−Removed: ACT-709478, an inhibitor of T-type calcium channels for the treatment of epilepsy, is covered by U.S.
−Removed: US 9,932,314 which expires in 2035 (not including a potential patent term extension of up to an additional five years).
−Removed: Our new VMAT2 inhibitor for the treatment of neurological and psychiatry disorders is covered by a patent application that has an earliest priority date in 2017.
−Removed: The terms of any patent that may issue from this patent application should be capable of continuing until 2038 in most jurisdictions without taking into account any patent term adjustment or extension regime.
−Removed: In addition to the potential patent term extensions referenced above, the products and product candidates in our pipeline may be subject to additional terms of exclusivity that we might obtain by virtue of later filed patent applications.
+Added: 10,905,690, which expires in 2035 (not including a potential patent term extension of up to an additional five years).
+Added: • NBI-1065844, a DAAO inhibitor for the treatment of negative symptoms of schizophrenia, is covered by U.S.
+Added: 9,290,456, among others, which expires in 2032 (not including a potential patent term extension of up to an additional five years).
+Added: • NBI-827104, an inhibitor of T-type calcium channels for the treatment of CSWS epilepsy, is covered by U.S.
+Added: US 9,932,314, among others, which expires in 2035 (not including a potential patent term extension of up to an additional five years).
+Added: • NBI-921352, an inhibitor of the Nav1.6 voltage-gated sodium channel for the treatment of SCN8A-DEE epilepsy, is covered by U.S.
+Added: US 10,246,453, among others, which expires in 2037 (not including a potential patent term extension of up to an additional five years).
+Added: • Elagolix, our small molecule GnRH antagonist under further development for the treatment of polycystic ovary syndrome, is covered by six of the issued U.S.
+Added: patents that are listed in the FDA’s Orange Book entry for ORILISSA and are set to expire between 2021 to 2024 (not including a potential patent term extension of up to an additional five years for one of the patents).
+Added: • NBI-1065845, a positive allosteric modulator of AMPA for the treatment of treatment-resistant depression is covered by U.S.
+Added: 8,778,934, among others, which expires in 2031 (not including a potential patent term extension of up to an additional five years).
+Added: • NBI-1065846, a GPR139 agonist for the treatment of anhedonia in depression, is covered by U.S.
+Added: 9,556,130, among others, which expires in 2035 (not including a potential patent term extension of up to an additional five years).
+Added: In addition to the potential patent term extensions referenced above, the products and product candidates in our pipeline may be subject to additional terms of exclusivity that we might obtain by future patent issuances.
Separately, the U.S., the European Union, or EU, and Japan all provide data and marketing exclusivity for new medicinal compounds.
If this protection is available, no competitor may use the original applicant’s data as the basis of a generic marketing application during the period of data and marketing exclusivity, which is measured from the date of marketing approval by the FDA or corresponding foreign regulatory authority.
−Removed: This period of exclusivity is generally five years in the U.S., six years in Japan and ten years in the EU, except that for biologics such as NBIb-1817, this period of exclusivity in the U.S.
+Added: This period of exclusivity is generally five years in the U.S., six years in Japan and ten years in the EU, except that for biologics, this period of exclusivity in the U.S.
is twelve years under the Biologics Price Competition and Innovation Act.
3 unchanged sentences
We currently rely on, and intend to continue to rely on, third-party manufacturers for the production of INGREZZA and our product candidates.
−Removed: In addition, we rely on third-party service providers to perform a variety of functions related to the packaging, storage and distribution of INGREZZA.
−Removed: We believe our outsource manufacturing strategy enables us to direct our financial resources to the maximization of our opportunity with INGREZZA, investment in our internal R&D programs and expansion of our clinical pipeline through business development opportunities.
Raw materials, active pharmaceutical ingredients, or API, and other supplies required for the production of INGREZZA and our product candidates are procured from various third-party manufacturers and suppliers in quantities adequate to meet our needs.
Continuing adequate supply of such raw materials and API is assured through our long-term commercial supply and manufacturing agreements with multiple manufacturers and our continued focus on the expansion and diversification of our third-party manufacturing relationships.
+Added: In addition, under the terms of our agreement with BIAL, we rely on BIAL and its suppliers to supply all drug product for the commercialization of ONGENTYS.
+Added: We believe our outsource manufacturing strategy enables us to direct our financial resources to the maximization of our opportunities with INGREZZA and ONGENTYS, investment in our internal R&D programs and expansion of our clinical pipeline through business development opportunities.
Our third-party manufacturers, suppliers and service providers may be subject to routine current Good Manufacturing Practice, or cGMP, inspections by the FDA or comparable agencies in other jurisdictions.
1 unchanged sentence
Marketing, Sales and Distribution
−Removed: Our specialty sales force for INGREZZA in the U.S.
−Removed: consists of approximately 250 experienced sales professionals primarily focused on educating health care professionals who treat patients with TD, including psychiatrists, neurologists, physician’s assistants and nurse practitioners.
−Removed: Our customers in the U.S.
−Removed: consist of a limited network of specialty pharmacy providers, which delivers INGREZZA to patients by mail, and a specialty distributor, which distributes INGREZZA primarily to closed-door pharmacies and government facilities.
−Removed: For 2019, our two largest customers accounted for approximately 86% of our gross product sales.
+Added: Our sales force in the U.S.
+Added: consists of approximately 250 experienced sales professionals focused on educating health care professionals, including psychiatrists and neurologists, who treat patients with tardive dyskinesia and Parkinson’s disease.
+Added: For INGREZZA, our customers in the U.S.
+Added: consist of a limited network of specialty pharmacy providers that deliver INGREZZA to patients by mail and a specialty distributor that distributes INGREZZA primarily to closed-door pharmacies and government facilities.
+Added: For ONGENTYS, our customers in the U.S.
+Added: consist primarily of wholesale distributors.
+Added: We rely on third-party service providers to perform a variety of functions related to the packaging, storage and distribution of INGREZZA and ONGENTYS.
Government Regulation
11 unchanged sentences
The Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors 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.
−Removed: In addition, we may be subject to HIPPA privacy and security regulations, which require the adoption of administrative, physical and technical safeguards to protect individually identifiable health information.
−Removed: The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare and Medicaid Services, or CMS, information related to payments or other transfers of value made to physicians, as defined by such law, and teaching hospitals, and applicable entities to report ownership and investment interests held by the physicians and their immediate family members.
+Added: In addition, we may be subject to HIPPA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their privacy and security regulations, which impose certain obligations, including the adoption of administrative, physical and technical safeguards to protect individually identifiable health information on covered entities subject to HIPPA (i.e., health plans, healthcare clearinghouses and certain healthcare providers) and their business associates that perform certain services for or on their behalf involving the use or disclosure of individually identifiable health information as we as their covered subcontractors.
+Added: The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare and Medicaid Services, or CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and applicable entities to report ownership and investment interests held by the physicians and their immediate family members.
+Added: Beginning in 2022, such obligations will include payments and other transfers of value provided in the previous year to certain other healthcare professionals, including physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified nurse anesthetists, and certified nurse-midwives.
Also, many states have similar healthcare statutes or regulations that may be broader in scope and may apply regardless of payor.
3 unchanged sentences
Preclinical studies generally are conducted in laboratory animals to evaluate the potential safety and efficacy of a product.
−Removed: Drug developers submit the results of preclinical studies to the FDA as a part of an IND application before clinical trials can begin in humans.
+Added: Drug developers submit the results of preclinical studies to the FDA as a part of an investigational new drug, or IND, application before clinical trials can begin in humans.
Typically, clinical evaluation involves a time consuming and costly three-phase process.
−Removed: Clinical trials are conducted with a small number of subjects to determine the early safety profile, maximum tolerated dose and pharmacokinetic properties of the product in human volunteers and for certain products, such as gene therapies, in patients with the target disease.
−Removed: Clinical trials are conducted with groups of patients afflicted with a specific disease in order to determine preliminary efficacy, optimal dosages and expanded evidence of safety.
−Removed: Larger, multi-center, comparative clinical trials are conducted with patients afflicted with a specific disease in order to determine safety and efficacy as primary support for regulatory approval by the FDA to market a product candidate for a specific disease.
+Added: Phase I Clinical trials are conducted with a small number of subjects to determine the early safety profile, maximum tolerated dose and pharmacokinetic properties of the product in human volunteers and for certain products, such as gene therapies, in patients with the target disease.
+Added: Phase II Clinical trials are conducted with groups of patients afflicted with a specific disease in order to determine preliminary efficacy, optimal dosages and expanded evidence of safety.
+Added: Phase III Larger, multi-center, comparative clinical trials are conducted with patients afflicted with a specific disease in order to determine safety and efficacy as primary support for regulatory approval by the FDA to market a product candidate for a specific disease.
The FDA closely monitors the progress of each of the three phases of clinical trials that are conducted in the U.S.
and may, at its discretion, re-evaluate, alter, suspend or terminate the testing based upon the data accumulated to that point and the FDA’s assessment of the risk/benefit ratio to the patient.
−Removed: Institutional Review Boards, Institutional Ethics Committees, and Data Safety Monitoring Boards may also place holds on our clinical trials or recommend that we voluntarily do so.
+Added: Institutional Review Boards, Institutional Ethics Committees, and Data Safety Monitoring Boards also closely monitor the conduct of our trials and may also place holds on our clinical trials or recommend that we voluntarily do so.
Clinical trials conducted in foreign countries are also subject to oversight by regulatory authorities in those countries.
1 unchanged sentence
In most cases, the submission of an NDA or BLA is subject to a substantial application user fee.
−Removed: Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of filing of a standard NDA for a new molecular entity to review and act on the submission.
+Added: Under the Prescription Drug User Fee Act, or PDUFA, the FDA has a goal of ten months from the date of filing of a standard NDA for a new molecular entity to review and act on the submission.
+Added: The FDA generally has a six-month review goal of priority NDAs.
In addition, under the Pediatric Research Equity Act of 2003 as amended and reauthorized, certain applications or supplements to an application must contain data that are adequate to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults or full or partial waivers from the pediatric data requirements.
−Removed: The FDA also may require submission of a risk evaluation and mitigation strategy plan to ensure that the benefits of the drug outweigh its risks.
−Removed: The risk evaluation and mitigation strategy plan could include medication guides, physician communication plans, assessment plans, and/or elements to assure safe use, such as restricted distribution methods, patient registries, or other risk minimization tools.
+Added: The FDA also may require submission of a risk evaluation and mitigation strategy to ensure that the benefits of the drug outweigh its risks.
+Added: The risk evaluation and mitigation strategy could include medication guides, physician communication plans, assessment plans, and/or additional elements to assure safe use, such as restricted distribution methods, patient registries, or other risk minimization tools.
The FDA conducts a preliminary review of all NDAs and BLAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review.
1 unchanged sentence
Once the submission is accepted for filing, the FDA begins an in-depth substantive review.
−Removed: The FDA reviews an NDA or BLA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.
+Added: The FDA reviews an NDA or BLA to determine, among other things, whether the drug is safe and effective for its intended use and whether the facility in which it is
+Added: manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.
The FDA may refer an application for a novel drug to an advisory committee.
11 unchanged sentences
The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
−Removed: approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.
+Added: After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.
We will also have to complete an approval process similar to that in the U.S.
4 unchanged sentences
The resulting prices may not be sufficient to generate an acceptable return to us or our corporate collaborators.
+Added: In the EU, there are currently two potential tracks for seeking marketing approval for a product not authorized in any EU member state:
+Added: a decentralized procedure and a centralized procedure.
+Added: In the decentralized procedure, identical applications for marketing authorization are submitted simultaneously to the national regulatory agencies.
+Added: Regulatory review is led by one member state (the reference-member state), and its assessment—based on safety, quality and efficacy—is reviewed and approved (assuming there are no concerns that the product poses a serious risk to public health) by the other member states from which the applicant is seeking approval (the concerned-member states).
+Added: The decentralized procedure leads to a series of single national approvals in all relevant countries.
+Added: In the centralized procedure, which is required of all products derived from biotechnology, a company submits a single marketing authorization application to the European Medicines Agency, or EMA, which conducts an evaluation of the dossier, drawing upon its scientific resources across Europe.
+Added: If the drug product is proven to fulfill the requirements for quality, safety and efficacy, the EMA’s Committee for Medicinal Products of Human Use, or CHMP, adopts a positive opinion, which is transmitted to the European Commission for final decision on grant of the marketing authorization.
+Added: While the EC generally follows the CHMP’s opinion, it is not bound to do so.
+Added: Subsequent commercialization is enabled by country-by-country reimbursement approval.
Orphan Drug Designation
22 unchanged sentences
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in mandatory revisions to the approved labeling to add new safety information;
−Removed: imposition of post-market studies or clinical trials to assess new safety risks;
−Removed: or imposition of distribution or other restrictions under a risk evaluation and mitigation strategies program.
+Added: imposition of post-market studies or clinical trials to assess
+Added: new safety risks;
+Added: or imposition of distribution or other restrictions under a risk evaluation and mitigation strategy program.
Other potential consequences include, among other things:
50 unchanged sentences
Any reduction in reimbursement from Medicare or other government-funded programs may result in a similar reduction in payments from private third-party payor.
−Removed: Some of the provisions of the ACA have yet to be fully implemented, and there have been legal and political challenges to certain aspects of the ACA.
−Removed: Since January 2017, the current presidential administration has signed two executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the ACA.
−Removed: Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the ACA.
−Removed: Legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act, includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”.
−Removed: In addition, the 2020 federal spending package permanently eliminates, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminates the health insurer tax.
+Added: There remain legal and political challenges to certain aspects of the ACA.
+Added: Since January 2017, the Trump administration signed several executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the ACA.
+Added: Concurrently, Congress considered legislation that would repeal or repeal and replace all or part of the ACA.
+Added: Legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act, includes a provision that repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”.
+Added: In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminated the health insurer tax.
On December 14, 2018, a Texas U.S.
2 unchanged sentences
Court of Appeals for the 5 th Circuit ruled that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the ACA are invalid as well.
−Removed: It is unclear how this decision, future decisions, subsequent appeals, and other efforts to repeal and replace the ACA will impact the ACA.
+Added: Supreme Court is currently reviewing this case, although it is unclear when a decision will be made.
+Added: It is also unclear how such litigation will impact the ACA.
Other legislative changes have been proposed and adopted since the ACA was enacted.
−Removed: These changes include, among others, aggregate reductions to Medicare payments to providers of up to 2% per fiscal year pursuant to the Budget Control Act of 2011, which began in 2013 and will remain in effect through 2029 unless additional Congressional action is taken.
+Added: These changes include, among others, aggregate reductions to Medicare payments to providers of up to 2% per fiscal year pursuant to the Budget Control Act of 2011, which began in 2013 and will remain in effect through 2030, except for a temporary suspension from May 1, 2020 through May 31, 2021 due to the COVID-19 pandemic, unless additional Congressional action is taken.
Also, there has been heightened governmental scrutiny recently over pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.
−Removed: Such scrutiny has resulted in several recent Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.
−Removed: At the federal level, the current presidential administration’s budget proposal for fiscal year 2020 contains further drug price control measures that could be enacted during the 2020 budget process or in other future legislation.
−Removed: Additionally, the current presidential administration released a “Blueprint” to lower drug prices and reduce out-of-pocket costs of drugs.
−Removed: Department of Health and Human Services has solicited feedback on some of these measures and, at the same, has implemented others under its existing authority.
−Removed: Although a number of these, and other measures may require additional authorization to become effective, Congress and the current presidential administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.
+Added: Such scrutiny has resulted in several Congressional hearings and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.
+Added: Both the U.S.
+Added: House of Representatives and the Senate Finance Committee passed legislation in 2019 to reform pharmaceutical pricing in a variety of meaningful ways, and we expect legislative efforts to reform drug pricing to continue in 2021.
+Added: At the federal level, the Trump administration’s budget proposal for fiscal year 2021 included a $135 billion allowance to support legislative proposals seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs.
+Added: On March 10, 2020, the Trump administration sent “principles” for drug pricing to Congress, calling for legislation that would, among other things, cap Medicare Part D beneficiary monthly out-of-pocket expenses, and place limits on pharmaceutical price increases.
+Added: Additionally, the Trump administration previously released a “Blueprint” to lower drug prices and reduce out-of-pocket costs of drugs.
+Added: On July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to drug pricing that sought to implement several of the administration’s proposals.
+Added: As a result, the FDA released a final rule on September 24, 2020, effective November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.
+Added: This rule is undergoing legal challenge.
+Added: Further, on November 20, 2020, HHS finalized 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.
+Added: 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.
+Added: This rule has been stayed until 2023 while pending litigation is heard in the courts.
+Added: On November 20, 2020, CMS issued an interim final rule implementing President Trump’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021.
+Added: On December 28, 2020, the United States District Court in Northern California issued a nationwide preliminary injunction against implementation of the interim final rule.
+Added: Two additional lawsuits in other jurisdictions are challenging the legality of this rule.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
+Added: Further, it is possible that additional governmental action is taken in response to the COVID-19 pandemic.
The biotechnology and pharmaceutical industries are subject to rapid and intense technological change.
1 unchanged sentence
Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approval and marketing than we do.
−Removed: Competition may also arise from, among other things, new drug development technologies, new or improved treatment options for preventing or reducing the incidence of disease in diseases our products treat and new small molecule or other classes of therapeutic agents.
+Added: Competition may also arise from, among other things, new drug development technologies, new or improved treatment options for preventing or reducing the incidence of disease in diseases our products treat and new small
+Added: molecule or other classes of therapeutic agents.
Such developments by competitors could reduce or eliminate the use of our products or may limit the utility and application of ongoing clinical trials for our product candidates.
1 unchanged sentence
Tardive Dyskinesia.
−Removed: INGREZZA competes with AUSTEDO (deutetrabenazine), which was approved by the FDA for the treatment of TD in adults in August 2017 and is marketed by Teva Pharmaceutical Industries, and a number of commercially available medicines used to treat TD off-label, such as tetrabenazine (Xenazine ® and generic equivalents), botulinum toxin, and various antipsychotic medications, benzodiazepines and anticholinergics.
−Removed: We are also aware of several clinical development-stage programs that, if successfully developed and approved, may compete with INGREZZA in the TD market.
−Removed: Endometriosis
−Removed: ORILISSA competes with several FDA-approved products for the treatment of endometriosis, uterine fibroids, infertility, and central precocious puberty.
−Removed: Additionally, there is also competition from surgical interventions.
−Removed: Over 100,000 hysterectomies are performed in
−Removed: annually as a direct result of endometriosis, as well as a significant number of laparoscopic procedures to ablate endometrial explants.
−Removed: Separate from these options, there are many programs in clinical development which serve as potential future competition.
−Removed: Lastly, there are numerous medicines used to treat the symptoms of disease (vs endometriosis directly) which may also serve as competition:
−Removed: oral contraceptives, nonsteroidal anti-inflammatory drugs, or NSAIDs and other pain medications including opioids.
+Added: INGREZZA competes with AUSTEDO (deutetrabenazine), which was approved by the FDA for the treatment of tardive dyskinesia in adults in August 2017 and is marketed by Teva Pharmaceutical Industries, and several clinical development-stage programs targeting tardive dyskinesia and related movement disorders.
+Added: Additionally, there are a number of commercially available medicines used to treat tardive dyskinesia off-label, such as Xenazine ® (tetrabenazine) and generic equivalents, and various antipsychotic medications (e.g., clozapine), anticholinergics, benzodiazepines (off-label), and botulinum toxin.
Parkinson’s Disease.
−Removed: Opicapone would currently compete directly with two FDA-approved COMT inhibitors and their generic equivalents.
−Removed: In addition, there are a number of alternative adjunctive treatment options (FDA-approved and in clinical development) for Parkinson’s disease patients which would compete with opicapone, including but not limited to various L-dopa preparations, dopamine agonists, MAO-B inhibitors.
−Removed: We are also aware of several programs in late-stage clinical development that may compete with opicapone.
+Added: ONGENTYS competes with two other FDA-approved COMT inhibitors and their generic equivalents.
+Added: Additionally, there are a number of alternative adjunctive treatment options (FDA-approved and in clinical development) for Parkinson’s patients which compete with ONGENTYS, including various L-dopa preparations, dopamine agonists, MAO-B inhibitors and others.
+Added: In terms of potential future competition, there are several programs in late-stage clinical development.
+Added: Endometriosis and Uterine Fibroids.
+Added: ORILISSA and ORIAHNN each compete with several FDA-approved products for the treatment of endometriosis, uterine fibroids, infertility, and central precocious puberty.
+Added: Additionally, there is also competition from surgical intervention, including hysterectomies and ablations.
+Added: Separate from these options, there are many programs in clinical development which serve as potential future competition.
+Added: Lastly, there are numerous medicines used to treat the symptoms of disease (vs.
+Added: endometriosis or uterine fibroids directly) which may also serve as competition:
+Added: oral contraceptives, NSAIDs and other pain medications including opioids.
Congenital Adrenal Hyperplasia.
1 unchanged sentence
alone, there are more than two dozen companies manufacturing steroid-based products.
−Removed: In addition, there are several companies developing medicinal treatments for CAH.
−Removed: Our investigational therapies may in the future compete with numerous approved products and development-stage programs being pursued by several companies.
−Removed: Our investigational gene therapies may in the future compete with numerous approved products and development-stage programs being pursued by several companies.
−Removed: As of December 31, 2019, we had approximately 700 full-time employees.
−Removed: None of our employees are represented by a collective bargaining arrangement, and we believe our relationship with our employees is good.
−Removed: We maintain product liability insurance coverage for INGREZZA and our clinical trials in amounts consistent with industry standards.
−Removed: However, insurance coverage is becoming increasingly expensive, and we may not be able to obtain or maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability.
+Added: In addition, there are several clinical development-stage programs targeting CAH and several companies developing medicinal treatments for CAH.
+Added: Our investigational treatments for potential use in epilepsy may in the future compete with numerous approved anti-seizure medications, or ASMs, and development-stage programs being pursued by several other companies.
+Added: Commonly used ASMs, among others, include phenytoin, levetiracetam, brivaracetam, cenobamate, carbamazepine, clobazam, lamotrigine, valproate, oxcarbazepine, topiramate, lacosamide, perampanel and cannabidiol.
+Added: There are currently no FDA-approved treatments specifically indicated for the early infantile epileptic encephalopathies SCN8A-DEE and EE-CSWS;
+Added: however, a number of different ASMs are currently used in these patient populations.
+Added: Schizophrenia.
+Added: The investigational treatment NBI-1065844 for the negative symptoms of schizophrenia may in the future compete with off-label antipsychotic and antidepressant medicines, including cariprazine, clozapine, fluoxetine, citalopram, sertraline, and amisulpride.
+Added: In addition, there are several development-stage programs being pursued by other companies, including pimavanserin, roluperidone, RO6889450 and sodium benzoate.
+Added: Currently, there are no-FDA approved treatments specifically indicated for the negative symptoms of schizophrenia.
+Added: Our investigational treatments for potential use in endocrinology, neurology, and psychiatry, as well as our investigational gene therapies, may in the future compete with numerous approved products and development-stage programs being pursued by several other companies.
+Added: Human Capital
+Added: Our Employees.
+Added: We have grown to a team of over 845 employees as of December 31, 2020, all of whom were employed in the U.S.
+Added: Our highly qualified and experienced team which includes scientists, physicians and professionals across sales, marketing, manufacturing, regulatory, finance and other important functions are critical to our success.
+Added: We also leverage temporary workers to provide flexibility for our business needs.
+Added: During 2020, we added 191 new employees to our team.
+Added: We expect to continue to add additional employees in 2021 with a focus on expanding our expertise and bandwidth in clinical and preclinical research and development.
+Added: We continually evaluate our business needs and opportunities
+Added: and balance in house expertise and capacity with external expertise and capacity.
+Added: Currently, we rely on third-party contract manufacturers.
+Added: The success of our human capital management investments is evidenced by our low employee turnover, a number which is regularly reviewed by our Board of Directors as part of their oversight of our human capital strategy.
+Added: In recognition of our efforts, in 2020, we were named to the Fortune Best Small and Medium Workplaces 2020 list ranking Number 8 across the country.
+Added: We were also named a Great Place to Work Certified company and were recognized on Great Place to Work’s Best Workplace for Parents 2020 list.
+Added: Employee Engagement, Talent Development & Benefits.
+Added: We believe that our future success largely depends upon our continued ability to attract and retain highly skilled employees.
+Added: We provide our employees with competitive salaries and bonuses, opportunities for equity ownership, development programs that enable continued learning and growth and a robust employment package that promotes well-being across all aspects of their lives, including health care, retirement planning and paid time off.
+Added: As part of our promotion and retention efforts, we also invest in ongoing leadership development through programs as well as offer tuition reimbursement.
+Added: In addition, we regularly conduct an employee survey to gauge employee engagement and identify areas of focus.
+Added: Diversity & Inclusion.
+Added: Much of our success is rooted in the diversity of our teams and our commitment to inclusion.
+Added: We value diversity at all levels and continue to focus on extending our diversity and inclusion initiatives across our entire workforce.
+Added: We believe that our business benefits from the different perspectives a diverse workforce brings, and we pride ourselves on having a strong, inclusive and positive culture based on our shared mission and values.
Corporate Information
6 unchanged sentences
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.