Vigabatrin

PARSIPPANY, N.J.--(BUSINESS WIRE)-- Pyros Pharmaceuticals, Inc. (Pyros or the Company), a leader in the development of enhanced specialty pharmaceuticals for rare diseases, announced today that the U.S. Food and Drug Administration (FDA) has approved VIGAFYDE™, the only ready-to-use vigabatrin oral solution. VIGAFYDE™ (vigabatrin) oral solution, is indicated as a monotherapy for the treatment of pediatric patients 1 month to 2 years of age with infantile spasms (IS), where the potential benefits outweigh the potential risk of vision loss. Please see full Prescribing Information below to view Important Safety Information, including BOXED WARNINGS. Infantile spasms, a rare but severe form of epilepsy, poses significant challenges for patients and their families. Pyros is committed to providing dependable services and an affordable treatment option to help ensure that families facing an IS diagnosis, and whose children are prescribed vigabatrin can quickly obtain this essential therapy. "The approval of VIGAFYDE™ marks the first new drug indicated for infantile spasms in fifteen years and underscores our unwavering commitment to supporting families facing this challenging condition," stated Michael Smith, co-founder and Chief Executive Officer of Pyros. “This is a momentous day for patients and caregivers who have long awaited the first ready-to-use vigabatrin. I believe this approval will bring renewed energy and momentum to the infantile spasms community, enhancing our efforts to improve disease education, develop care pathways, and expand investment in infantile spasms research,” stated Edwin Urrutia, co-founder and Chief Operating Officer at Pyros. VIGAFYDE™ is expected to be available in the second half of 2024. Additionally, Pyros Total Care™, the Company’s personalized comprehensive support program, is available to assist families throughout the treatment journey. About Pyros Total Care™ As part of the Company’s commitment to prioritizing patient access to treatments for those who need them most, Pyros provides ongoing personalized support to caregivers through Pyros Total Care™ for those prescribed VIGAFYDE™. The support program offers personal assistance and financial resources to caregivers whose child is starting or continuing therapy. Our dedicated support team includes a nurse educator, reimbursement support, and a clinical pharmacist. For more information, visit PyrosTotalCare.com or call 1-888-760-8330, Monday to Friday, 8 a.m. to 5 p.m. Central Time. About Infantile Spasms Infantile spasms (IS) is a rare, severe form of epilepsy that typically begins in children less than one year old.1 Infantile spasms can appear as subtle but repetitive movements that can often be overlooked or misdiagnosed. IS can lead to long-term permanent issues such as continued seizures, other forms of epilepsy, autism spectrum disorder, and developmental issues.2 The American Academy of Neurology conducted a systematic review of treatment for IS and concluded that successful treatment of IS can improve the long-term prognosis.3 About Vigabatrin Vigabatrin is a medication used in the treatment of infantile spasms and is designed to inhibit the enzyme GABA transaminase, consequently increasing gamma-aminobutyric acid (GABA) levels in the brain.4,5 This release is thought to enhance seizure control for patients by modulating neuronal excitability.6 Vigabatrin's mechanism of action underscores its importance in treating seizure disorders.7 Its impact may extend beyond seizure management, with emerging research indicating potential benefits in mitigating neurodevelopmental complications associated with certain epilepsy syndromes.8 Vigabatrin REMS The U.S. FDA has approved a single shared system Risk Evaluation and Mitigation Strategy (REMS) for all vigabatrin products called the Vigabatrin REMS. This strategy is mandated by the FDA to ensure that patients and healthcare providers make informed risk-benefit decisions before starting treatment, and to ensure the proper use of vigabatrin throughout the treatment process. Healthcare providers must be certified in the Vigabatrin REMS to prescribe VIGAFYDE™, and patients must be enrolled in the Vigabatrin REMS to receive VIGAFYDE™. Once certified and enrolled, prescribers and patients remain in the Vigabatrin REMS and do not need to undergo recertification or re-enrollment. INDICATION VIGAFYDE™ (vigabatrin) is indicated as monotherapy for the treatment of infantile spasms in pediatric patients 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss. IMPORTANT SAFETY INFORMATION FOR VIGAFYDE™ (vigabatrin) WARNING: PERMANENT VISION LOSS See full Prescribing Information for complete BOXED WARNING. VIGAFYDE can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, VIGAFYDE may also decrease visual acuity. Risk increases with increasing dose and cumulative exposure, but there is no dose exposure to VIGAFYDE known to be free of risk of vision loss. Risk of new and worsening vision loss continues as long as VIGAFYDE is used, and possibly after discontinuing VIGAFYDE. Baseline and period vision assessment is recommended for patients on VIGAFYDE. However, this assessment cannot always prevent vision damage. VIGAFYDE is available only through a restricted program called the Vigabatrin REMS. WARNINGS AND PRECAUTIONS VIGAFYDE can cause permanent vision loss. Because of this risk and because VIGAFYDE, when it is effective, provides an observable symptomatic benefit; patient response and continued need for treatment should be periodically assessed. Monitoring of vision by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina is recommended. Because vision testing in infants and children is difficult, vision loss may not be detected until it is severe. VIGAFYDE is not approved for use in pediatric patients older than 2 years of age or in adults. Due to the risk of permanent vision loss, VIGAFYDE is only available through the Vigabatrin REMS. Further information is available at or 1-866-244-8175. Abnormal Magnetic Resonance Imaging (MRI) signal changes and Intramyelinic Edema (IME) in some infants and young children treated with vigabatrin have been observed. These changes generally resolved with discontinuation of treatment and resolved in a few patients despite continued use. VIGAFYDE should be withdrawn gradually to avoid withdrawal seizures. Patients and caregivers should be told not to suddenly discontinue VIGAFYDE therapy. Monitor for symptoms of anemia. VIGAFYDE causes somnolence and fatigue. In pediatric clinical trials (pooled data), the incidence of peripheral neuropathy and edema observed in pediatric patients was similar on vigabatrin and placebo. VIGAFYDE causes weight gain in pediatric patients. ADVERSE REACTIONS Most common (≥10%) adverse reactions in patient receiving low-dose (18-36 mg/kg/day) vs high-dose (100-148 mg/kg/day) vigabatrin, respectively, were upper respiratory tract infection (51%, 46%), otitis media (44%, 30%), fever (29%, 19%), viral infection (20%, 19%), sedation (19%, 17%), somnolence (17%, 19%), irritability (16%, 23%), constipation (14%, 12%), vomiting (14%, 20%), diarrhea (13%, 12%), nasal congestion (13%, 4%), pneumonia (13%, 11%), insomnia (10%, 12%), ear infection (7%, 14%), and rash (8%, 11%). You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088 or Pyros at 1-855-406-1010. Please see full Prescribing Information, including BOXED WARNING, for additional Important Safety Information. About Pyros Pyros Pharmaceuticals is developing enhanced specialty pharmaceuticals for rare diseases. Our mission is to elevate the standard of care for infantile spasms, providing treatment options that significantly improve the lives of affected children. Through our enhanced therapies and comprehensive support services, we aim to assist providers and caregivers in navigating the complexities of the patient journey. For more information, please visit: Forward-Looking Statements The Company has made statements throughout this press release which constitute forward-looking statements. These statements involve known and unknown risks, uncertainties and other factors that may cause its actual results, levels of activity, performance or achievements to be materially different from any results, levels of activity, performance or achievements expressed or implied by any such forward-looking statements. In some cases you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “expect,” “hopes,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “likely,” “potential,” or “continue” or the negative of these terms and similar words. Although management believe that the expectations reflected in these forward-looking statements are reasonable, management cannot guarantee future results, levels of activity, performance or achievements. Furthermore, management undertakes no obligation to update any forward-looking statements for any reason unless required to do so by law. References Mackay, M. T., Weiss, S. K., Adams-Webber, T., et al. (2004). Practice parameter: medical treatment of infantile spasms. Report of the American Academy of Neurology and the Child Neurology Society. Neurology, 62(10), 1668-1681. Lux, A. L., & Osborne, J. P. (2004). A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group. Epilepsia, 45(11), 1416-1428. Pellock, J. M., Hrachovy, R., Shinnar, S., et al. (2010). Infantile spasms: a U.S. consensus report. Epilepsia, 51(10), 2175-2189. Cilio, M. R., & Cross, H. J. (2011). Vigabatrin. Neurotherapeutics, 8(2), 330–337. Löscher, W., & Schmidt, D. (2004). New horizons in the development of antiepileptic drugs: innovative strategies. Epilepsy Research, 60(2–3), 77–159. Houston, S. M., & Smart, T. G. (2006). GABA pharmacology: the search for analgesics. Current Opinion in Investigational Drugs, 7(1), 48–55. Wheless, J. W. (2004). Vigabatrin: efficacy and safety in pediatric epilepsy. Journal of Child Neurology, 19(Suppl 1), S21–S29. Chiron, C. (2006). Vigabatrin in the treatment of epilepsy: literature review. Epileptic Disorders, 8(S1), S33–S38.

Takeda has completed two Phase 3 trials studying soticlestat as a treatment for Lennox-Gastaut syndrome and Dravet syndrome; topline data are anticipated in Takeda's H1 2024 fiscal yearA Phase 1, double-blind, multiple-ascending dose trial evaluating OV888 (GV101) is complete; topline safety data are expected in H1 2024Ovid expects to initiate a Phase 2 clinical program studying OV888 (GV101) in cerebral cavernous malformations in H2 2024Cash, cash equivalents and marketable securities were $90.3 million as of March 31, 2024; this capital is expected to support operations into H1 2026 NEW YORK, May 14, 2024 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (Nasdaq: OVID), a biopharmaceutical company dedicated to meaningfully improving the lives of people affected by rare epilepsies and brain conditions, today reported business updates and financial results for the first quarter ended March 31, 2024. "This is an exhilarating period for Ovid. Our innovative programs are progressing through clinical trials and moving closer to addressing the significant unmet needs of individuals with developmental and epileptic encephalopathies," stated Jeremy Levin, D.Phil, MB BChir., Chairman and CEO of Ovid Therapeutics. "Takeda has recently completed two critical Phase 3 studies of soticlestat for Dravet syndrome and Lennox-Gastaut syndrome, and we are eagerly anticipating the outcomes as soticlestat could herald a new class of anti-seizure medication. Our license agreement with Takeda provides us with significant potential near- and longer-term financial resources." "Furthermore, our collaboration with Graviton Bioscience has proven to be highly fruitful. We are on the brink of receiving the Phase 1 findings for our ROCK2 inhibition program and are planning to launch our Phase 2 study later this year, targeting cerebral cavernous malformations," Dr. Levin continued. Pipeline Updates Ovid pipeline programs are advancing on track. Multiple data and regulatory milestones are expected before year-end. These include: Soticlestat: Takeda has completed two pivotal Phase 3 trials studying soticlestat as a treatment for Lennox Gastaut syndrome (LGS) and Dravet syndrome (DS). Topline data for both trials are anticipated in Takeda's H1 2024 fiscal year (which is by or before September 2024). Takeda anticipates regulatory filings for soticlestat in its fiscal year 2024 (by or before March 31, 2025). 2024 American Academy of Neurology (AAN) meeting: Takeda presented seven poster presentations, which were originally presented at the 2023 American Epilepsy Society meeting. These posters support soticlestat's anticipated profile and mechanism of action, as well as the unmet need that persists in LGS and DS. Highlights included: Soticlestat is a potential first-in-class anti-seizure medicine with a mechanism of action that inhibits cholesterol 24 hydroxylase, reducing extra-synaptic glutamate, neuronal hyperexcitability, and seizure susceptibility.Soticlestat's metabolism has been well characterized, reflecting minimal concern of drug-to-drug interactions.Physiologically based pharmacokinetic models predicted that soticlestat has no clinically significant drug-to-drug interactions. Financial interest: Ovid co-developed soticlestat with Takeda through the completion of Phase 2 studies and subsequently sold its rights back to Takeda. Ovid retains significant financial interest in soticlestat. If soticlestat is approved and commercialized, Ovid is eligible to receive regulatory and commercial milestone payments of up to $660 million, as well as tiered, low double-digit royalties up to 20% on global net sales from Takeda. Of these potential future payments, Ovid sold a 13% interest to Ligand Pharmaceuticals for $30 million in October 2023. Ovid retains 87% of its interest in any milestone payments and royalties. Ovid has no ongoing obligations or costs associated with the development of soticlestat. OV888 (GV101): Ovid and its collaborator, Graviton Bioscience, have completed a Phase 1 multiple-ascending dose (MAD) study of OV888 (GV101), with topline safety data expected in H1 2024. No serious adverse events were observed in the Phase 1 study. OV888 (GV101) is a highly selective ROCK2 inhibitor for the potential treatment of cerebral cavernous malformations (CCM) and other rare neurological conditions. Ovid and Graviton expect to initiate a Phase 2 program evaluating the safety and efficacy of OV888 in H2 2024.OV329: Ovid is advancing two development programs (oral and intravenous) for OV329, a next-generation GABA-aminotransferase inhibitor for the potential treatment of chronic and acute seizures. Both programs are anticipated to have milestones this year and supportive preclinical findings. Oral formulation An oral formulation of OV329 for the potential treatment of chronic seizures is being evaluated in a Phase 1 safety study, which includes surrogate biomarkers to measure target engagement and clinical efficacy. The single-ascending dose portion is complete and no safety signals were observed. The multiple-ascending dose study is ongoing and is applying magnetic resonance spectrometry and transcranial magnetic stimulation as biomarkers of efficacy. Data are expected from the Phase 1 study in late 2024, as are further preclinical data characterizing OV329's safety profile relative to vigabatrin.Intravenous (IV) formulationAn IV formulation of OV329 for the potential treatment of acute seizures is on track for an anticipated IND application or an equivalent regulatory application by late 2024. Further preclinical data supporting OV329 for the treatment of status epilepticus are expected later this year. OV350 and portfolio of potassium chloride co-transporter 2 (KCC2) direct activators: Ovid is on track to submit an IV formulation of OV350 for an IND by year-end 2024. OV350 is the first program emerging from Ovid’s novel portfolio of KCC2 direct activators. The Company believes several of its direct activators have the potential to treat multiple diseases, including psychiatric and anticonvulsant indications, thereby enabling possible partnering and co-development opportunities. General Corporate & Business Updates Financial runway: Ovid anticipates its cash runway will support operations and clinical development programs into H1 2026. During this time, Ovid anticipates several events for its current pipeline programs as well as clinical and regulatory results for soticlestat from Takeda.Research & development strategy: Ovid is focused on the development of novel, targeted small molecules that have the potential to be first-in-class or best-in-class neurotherapeutics. The mechanisms of action in Ovid’s pipeline programs address biological targets implicated in neuronal hyperexcitability, vascular, and inflammatory disorders in the brain. The broad therapeutic potential of these mechanisms may enable future development and partnering in a range of neurological conditions, including seizures, psychiatric conditions, neurovascular and neurodegenerative diseases.Business development activities: Ovid’s future business development efforts are focused on: potential collaborations to advance development opportunities for its KCC2 portfolio in non-core indications; and the exploration of commercial opportunities for some of its programs in territories outside the United States. First Quarter 2024 Financial Results Cash, cash equivalents and marketable securities as of March 31, 2024 totaled $90.3 million.Revenue was $148,000 for the first quarter ended March 31, 2024, as compared to $66,000 in the same period in 2023. Revenues were the result of royalty and licensing agreements.Research and development expenses were $10.4 million for the first quarter ended March 31, 2024, compared to $6.6 million in the same period in 2023. The increase is related to advancement of Ovid's clinical pipeline as described above, including the addition of the OV888 (GV101) Phase 1 MAD program and expanded OV329 clinical development activities.General and administrative (G&A) expenses were $7.2 million for the first quarter ended March 31, 2024, as compared to $8.3 million for the same period in 2023, reflecting reductions of full time G&A employees made in 2023.Total operating expenses were $17.6 million for the first quarter ended March 31, 2024, as compared to $15.0 million for the same period last year.Ovid reported a net loss of $11.7 million, or basic and diluted net loss per share attributable to common stockholders of $0.17, for the first quarter of 2024, as compared to a net loss of $13.4 million, or basic and diluted net loss per share attributable to common stockholders of $0.19, for the same period in 2023. About Ovid Therapeutics Ovid Therapeutics Inc. is a New York-based biopharmaceutical company that is dedicated to meaningfully improving the lives of people affected by epilepsies and brain conditions. The Company is advancing a pipeline of novel, targeted small molecule candidates that modulate the intrinsic and extrinsic factors involved in neuronal hyperexcitability causative of seizures and other neurological symptoms. Ovid is developing: OV888 (GV101), a potent and highly selective ROCK2 inhibitor, for the potential treatment of lesions associated with cerebral cavernous malformations and other brain disorders; OV329, a GABA-aminotransferase inhibitor, a potential therapy for treatment-resistant seizures; and OV350, a direct activator of the KCC2 transporter, for the potential treatment of epilepsies and other psychiatric conditions. Ovid also maintains a significant financial interest in the future regulatory development and potential commercialization of soticlestat, which Takeda is responsible for advancing globally. Soticlestat is a cholesterol 24-hydroxylase inhibitor, which is currently in Phase 3 trials for DS and LGS. For more information about these and other Ovid research programs, please visit www.ovidrx.com. Forward-Looking Statements This press release includes certain disclosures by Ovid that contain “forward-looking statements,” including, without limitation: statements regarding the potential use and development of OV888 (GV101), OV329, OV350 and compounds from Ovid’s library of direct activators of KCC2; the potential therapeutic opportunity of OV888 (GV101), OV329, OV350 and compounds from Ovid’s library of direct activators of KCC2; the timing of data readout of topline safety data from Ovid’s Phase 1, double-blind, multiple-ascending dose trial evaluating OV888 (GV101); the timing of initiation of Ovid’s Phase 2 clinical program studying OV888 (GV101) in CCM; the potential opportunity for soticlestat; the timing and data readout of Takeda’s two pivotal Phase 3 trials evaluating soticlestat for DS and LGS; Ovid’s expectations regarding the duration of its cash runway and the expectation that it will support the advancement of Ovid’s pipeline and Ovid's potential future business development opportunities. You can identify forward-looking statements because they contain words such as “anticipates,” “expects,” “hope,” “intends,” “may,” “plan,” “potentially,” and “will,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances). Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, uncertainties inherent in the preclinical and clinical development and regulatory approval processes, risks related to Ovid’s ability to achieve its financial objectives, the risk that Ovid may not be able to realize the intended benefits of its technology or its business strategy, or risks related to Ovid’s ability to identify business development targets or strategic partners, to enter into strategic transactions on favorable terms, or to consummate and realize the benefits of any business development transactions. Additional risks that could cause actual results to differ materially from those in the forward-looking statements are set forth under the caption “Risk Factors” in Ovid’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”) on March 8, 2024, and in future filings Ovid makes with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Ovid assumes no obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Condensed Consolidated Statements of OperationsUnaudited (in thousands, except share and per share data)For The ThreeMonths EndedMarch 31, 2024 For The ThreeMonths EndedMarch 31, 2023Revenue: License and other revenue$148 $66 Total revenue 148 66 Operating expenses: Research and development 10,397 6,615 General and administrative 7,168 8,344 Total operating expenses 17,565 14,958 Loss from operations (17,417) (14,892)Other income (expense), net 5,723 1,536 Loss before provision for income taxes (11,694) (13,356)Provision for income taxes — — Net loss$(11,694) $(13,356)Net loss per share, basic$(0.17) $(0.19)Net loss per share, diluted$(0.17) $(0.19)Weighted-average common shares outstanding, basic 70,716,929 70,490,704 Weighted-average common shares outstanding, diluted 70,716,929 70,490,704 Select Condensed Consolidated Balance Sheet DataUnaudited (in thousands)March 31, 2024 December 31, 2023Cash, cash equivalents and marketable securities$90,259 $105,834Working capital(1) 84,267 98,123Total assets 131,613 144,027Total stockholder's equity 78,279 87,797(1)Working capital defined as current assets less current liabilities Contacts Investor RelationsGarret BonneyIR@ovidrx.com(617) 735-6093 MediaRaquel CaboRCabo@ovidrx.com(646) 647-6553