[Translation] An open, single-arm, prospective, multicenter post-marketing clinical study to evaluate the safety and efficacy of vigabatrin oral solution as a single drug in the treatment of infantile spasms in China

评价氨己烯酸口服溶液用散单药治疗中国婴儿痉挛的安全性和有效性

[Translation]

To evaluate the safety and efficacy of vigabatrin oral solution as a single drug for the treatment of infantile spasms in Chinese patients

Start Date26 Apr 2024

Sponsor / Collaborator

Dr. Reddy's Laboratories Ltd.

[+1]

CTRI/2022/12/048517

/ Not yet recruitingNot ApplicableIIT

Safety and efficacy of vigabatrin add on compared to placebo in Lennox-Gastaut Syndrome: A randomizedcontrolled trial

Start Date28 Dec 2022

Sponsor / Collaborator-

100 Clinical Results associated with Vigabatrin

100 Translational Medicine associated with Vigabatrin

100 Patents (Medical) associated with Vigabatrin

2,515

Literatures (Medical) associated with Vigabatrin

01 Dec 2024·EPILEPSY & BEHAVIOR

Evolving treatment strategies for early-life seizures in Tuberous Sclerosis Complex: A review and treatment algorithm

Review

Author: Samanta, Debopam

Tuberous sclerosis Complex (TSC) is a genetic disorder characterized by multisystem involvement, with epilepsy affecting 80-90% of patients, often beginning in infancy. Early-life seizures in TSC are associated with poor neurodevelopmental outcomes, underscoring the importance of timely and effective management. This review explores the evolving treatment landscape for TSC-associated seizures in young children, focusing on three recently approved or license-expanded therapies: vigabatrin, everolimus, and cannabidiol. The efficacy and safety profiles of these treatments are examined based on clinical trials and real-world evidence, with a focus on their use in treating seizures in young children. The preemptive use of vigabatrin in clinical studies has also been carefully reviewed. A treatment algorithm is proposed, emphasizing early diagnosis, prompt initiation of appropriate therapy, and a stepwise approach to managing both infantile spasms and focal seizures. The algorithm incorporates these newer therapies alongside traditional antiseizure medications and non-pharmacological approaches. Challenges in optimizing treatment strategies, minimizing side effects, and improving long-term outcomes are discussed. This review aims to guide clinicians in navigating the complex landscape of early-life seizures associated with TSC, ultimately striving for improved seizure control and better developmental outcomes in this vulnerable population.

05 Nov 2024·Toxicology Research

Upregulation of ACSL, ND75, Vha26 and sesB genes by antiepileptic drugs resulted in genotoxicity in drosophila

Article

Author: Nagaraj, K ; Shamapari, R

Abstract:

Clobazam (CLB) and Vigabatrin (VGB) are commonly used antiepileptic drugs (AEDs) in the treatment of epilepsy. Here, we have examined the genotoxic effect of these AEDs in Drosophila melanogaster. The Drosophila larvae were exposed to different concentrations of CLB and VGB containing food media. The assessment encompassed oxidative stress, DNA damage, protein levels, and gene expression profiles. In the CLB-treated group, a reduction in reactive oxygen species (ROS) and lipid peroxidation (LPO) levels was observed, alongside increased levels of superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO). Conversely, the VGB-treated group displayed contrasting results, with increased ROS and LPO and decreased SOD, CAT, and NO levels. However, both CLB and VGB induced DNA damage in Drosophila. Proteomic analysis (SDS-PAGE and OHRLCMS) in the CLB and VGB groups identified numerous proteins, including Acyl-CoA synthetase long-chain, NADH–ubiquinone oxidoreductase 75 kDa subunit, V-type proton ATPase subunit E, ADP/ATP carrier protein, malic enzyme, and DNA-binding protein modulo. These proteins were found to be associated with pathways like growth promotion, notch signaling, Wnt signaling, neuromuscular junction (NMJ) signaling, bone morphogenetic protein (BMP) signaling, and other GABAergic mechanisms. Furthermore, mRNA levels of ACSL, ND75, Vha26, sesB, and Men genes were upregulated in both CLB and VGB-treated groups. These findings suggest that CLB and VGB could have the potential to induce genotoxicity and post-transcriptional modifications in humans, highlighting the importance of monitoring their effects when used as AEDs.

01 Nov 2024·EPILEPSY RESEARCH

Serum matrix metallopeptidase-9 levels in infantile epileptic spasms syndrome of unknown etiology

Article

Author: Kikuchi, Kenjiro ; Takeuchi, Hirokazu ; Matsuura, Ryuki ; Hamano, Shin-Ichiro ; Hirata, Yuko ; Hamano, Shin-ichiro ; Takeda, Rikako ; Koichihara, Reiko ; Oka, Akira

PURPOSE:

Epileptic spasms are the primary symptom of infantile epileptic spasms syndrome (IESS); however, their direct impact on blood-brain barrier (BBB) function is unknown. Matrix metallopeptidase-9 (MMP-9), degrades type IV collagen, a key component of the blood-brain barrier, while tissue inhibitor of metalloproteinase-1 (TIMP-1) suppresses its activity, protecting BBB integrity. This study aimed to assess serum MMP-9 and TIMP-1 levels in patients with IESS of unknown etiology.

METHODS:

We prospectively assessed serum MMP-9 and TIMP-1 levels prior to administering vigabatrin or adrenocorticotropic hormone therapy in patients with IESS of unknown etiology at Saitama Children's Medical Center between February 2012 and December 2023. We compared these biomarkers between patients with epileptic spasms and age-matched controls and performed a curve regression analysis between the biomarkers and the frequency of epileptic spasms. Additionally, we assessed whether MMP-9 and TIMP-1 levels were diagnostic predictors of IESS.

RESULTS:

This study included 22 patients with IESS (11 males) and 12 controls. Serum MMP-9 and MMP-9/TIMP-1 ratios were higher in patients with IESS than in controls (p < 0.001 and p = 0.002, respectively). A high frequency of epileptic spasms also led to higher serum MMP-9 levels (y = 0.0871x² + 0.195x + 195.15, R² = 0.77, p < 0.001). Using MMP >188 ng/mL as the cutoff level, the sensitivity for diagnosing IESS was 95.5 %, the specificity was 75.0 %, the positive likelihood ratio was 3.82 (95 % confidence interval (CI) 1.43-10.22), and the relative risk was 8.75 (95 % CI 1.36-56.5).

CONCLUSION:

Patients with IESS had elevated serum MMP-9 levels, suggesting an association between epileptic spasms and blood-brain barrier dysfunction. MMP-9 level measurement may be useful for diagnosing suspected patients.

News (Medical) associated with Vigabatrin

02 Dec 2024

·www.prnewswire.com

UPSHER-SMITH TO FEATURE MULTIPLE PRESENTATIONS AT THE AMERICAN EPILEPSY SOCIETY (AES) 2024 ANNUAL MEETING

MAPLE GROVE, Minn., Dec. 2, 2024 /PRNewswire/ -- Upsher-Smith Laboratories, LLC (Upsher-Smith) today announced its participation at AES 2024, the Annual Meeting of the American Epilepsy Society, from December 6-10, 2024 in Los Angeles, California, where it will present a range of events, including Innovation Pavilion presentations and two scientific posters featuring new data on its medications for infantile spasms. Upsher-Smith's parent company, Bora Pharmaceuticals Co., Ltd., recently acquired US-based Pyros Pharmaceuticals Inc., a leader in the development of enhanced specialty pharmaceuticals for rare diseases. The acquisition added VIGAFYDE™ (vigabatrin) Oral Solution to Upsher-Smith's portfolio of rare disease medications, making it the third vigabatrin formulation to be offered by Upsher-Smith, alongside VIGADRONE® (vigabatrin) Powder for Oral Solution and Tablets. VIGAFYDE™ is the first and only ready-to-use vigabatrin oral solution and is indicated as monotherapy for the treatment of infantile spasms in pediatric patients 1 month to 2 years, where the potential benefits outweigh the potential risk of vision loss. VIGAFYDE™ is the first new drug application (NDA) approved for this condition in 15 years and represents a welcome expansion of vigabatrin treatment options, enabling customization of therapy to best meet the needs of individual patients and caregivers. Innovation Pavilion Presentations The Company also invites attendees to visit the Innovation Pavilion for informative presentations on vigabatrin between the hours of 12:30 pm – 1:30 pm on Saturday, December 7, 2024, Sunday, December 8, 2024, and Monday, December 9, 2024. The Innovation Pavilion is located in the exhibit hall (South Hall H, Level 1). Scientific Posters for Presentation Include: Dissolution and Stability of Vigabatrin Powder in Water, Fruit Juice, Milk, and Infant Formula Poster 2.407; Sunday, December 8, 2024; 10 a.m. – 4 p.m. PST Authors to present 12 p.m. to 2 p.m. Los Angeles Convention Center, South Lobby, Street Level, South Hall H, Level 1 Comparison of Vigabatrin Oral Solution Versus Vigabatrin (SABRIL®) Powder for Oral Solution in Infantile Spasms by Caregivers Poster 2.398; Sunday, December 8, 2024; 10 a.m. – 4 p.m. PST Authors to present 12 p.m. to 2 p.m. Los Angeles Convention Center, South Lobby, Street Level, South Hall H, Level 1 Abstracts of the poster presentations can be found online at . To schedule an interview with a study author, please contact Elizabeth Likly at [email protected]. Upsher-Smith representatives will also be available at its commercial booths throughout the conference to engage with clinicians about its products. Products include the new ready-to-use vigabatrin solution, VIGAFYDE™ at Booth #1439, and VIGADRONE® Powder for Oral Solution and Tablets and the Promise of Support™ Program, which has been providing comprehensive support to patients prescribed VIGADRONE® since 2018, at Booth #1627. About Upsher-Smith's Promise of Support™ Program Central to Upsher-Smith's commitment to rare disease communities is its Promise of Support™ Program, ensuring comprehensive assistance for patients, caregivers, and healthcare providers throughout the treatment journey. For nearly a decade, the program has offered resources for uninterrupted medication supply, prior authorization support, patient education materials, collaboration with a leading specialty pharmacy partner, and streamlined prescribing and enrollment procedures. It also includes copay assistance for eligible patients to help lessen the financial burden on patients and their families. To learn more about Upsher-Smith, its products, and the Promise of Support™ Program visit: . Vigabatrin REMS All vigabatrin products are governed by a Risk Evaluation and Mitigation Strategy (REMS) mandated by the FDA. The Vigabatrin REMS ensures that patients and healthcare providers make informed risk-benefit decisions about its use. Healthcare providers must be enrolled in the Vigabatrin REMS to prescribe these products, and patients must be enrolled to receive them. IMPORTANT SAFETY INFORMATION FOR VIGAFYDE™ (vigabatrin) What is the most important information I should know about VIGAFYDE? VIGAFYDE can cause serious side effects, including: Permanent vision loss: VIGAFYDE can damage the vision of anyone who takes it. Some babies can have severe loss, particularly to their ability to see to the side when they look straight ahead (peripheral vision). With severe vision loss, your baby may only be able to see things straight in front of them (sometimes called "tunnel vision"). Your baby also may have blurry vision. If this happens, it will not get better. Tell your healthcare provider right away if your baby might not be seeing as well as before starting VIGAFYDE or is acting differently than normal. Vision loss in babies: Because of the risk of vision loss, VIGAFYDE is used in babies 1 month to 2 years of age with infantile spasms only when you and your healthcare provider decide that the possible benefits of VIGAFYDE are more important than the risks. Parents or caregivers are not likely to recognize the symptoms of vision loss in babies until it is severe. Healthcare providers may not find vision loss in babies until it is severe. It is difficult to test vision in babies, but, to the extent possible, all babies should have their vision tested before starting VIGAFYDE or within 4 weeks after starting VIGAFYDE, and every 3 months after that until VIGAFYDE is stopped. Your baby also should have a vision test about 3 to 6 months after VIGAFYDE is stopped. Your healthcare provider will determine if your baby can be tested. If your baby cannot be tested, your healthcare provider may continue prescribing VIGAFYDE, but they will not be able to watch for any vision loss. Even if your baby's vision seems fine, it is important to get regular vision tests because damage can happen before your baby acts differently. Even these regular vision exams may not show the damage to your baby's vision before it is severe and permanent. All babies who take VIGAFYDE: Are at risk for permanent vision loss with any amount of VIGAFYDE. The risk of vision loss may increase with higher doses of VIGAFYDE, and the longer it is taken. It is not possible for your healthcare provider to know when vision loss will happen. It could happen soon after starting VIGAFYDE or any time during treatment. It may even happen after treatment has stopped. Because VIGAFYDE might cause permanent vision loss, it is available to healthcare providers and patients only under a special program called Vigabatrin Risk Evaluation and Mitigation Strategy (REMS). Your healthcare provider will explain the details of the Vigabatrin REMS to you. For more information, go to or call 1-866-244-8175. Magnetic resonance imaging (MRI) changes in babies with infantile spasms (IS): brain pictures taken by MRI show changes in some babies after they are given VIGAFYDE. It is not known if these changes are harmful. What are the possible side effects of VIGAFYDE? VIGAFYDE can cause serious side effects, including sleepiness (sleepy babies may have a harder time suckling and feeding or may be irritable) and weight gain without swelling. Serious side effects that happen in adults who take vigabatrin and are not known if they will happen in babies are low red blood cell counts, nerve problems, and swelling. Tell your baby's healthcare provider right away if your baby's seizures get worse. The most common side effects of VIGAFYDE in babies include sleepiness, ear infection, swelling of the bronchial tubes, and irritability. Tell your healthcare provider if your baby has any side effect that bothers them or that does not go away. These are not all the possible side effects of VIGAFYDE. Do not stop taking VIGAFYDE suddenly. This can cause serious problems. Talk to your healthcare provider for directions on how to stop treatment. What should I tell my healthcare provider before starting VIGAFYDE? Before giving VIGAFYDE to your baby for IS, inform your healthcare provider about all your baby's medical conditions. This includes whether your baby has ever had an allergic reaction to vigabatrin, such as hives, itching, or trouble breathing, as well as any history of vision problems, or kidney issues. Tell your healthcare provider about all the medicines your baby takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Interactions between VIGAFYDE and other medicines could lead to side effects. You may report side effects to the FDA at or call 1-800-FDA-1088 or Pyros at 1-855-406-1010. Please see full Prescribing Information, including BOXED WARNING, Medication Guide, and Instructions for Use for additional Important Safety Information. WHAT IMPORTANT SAFETY INFORMATION SHOULD I KNOW ABOUT VIGADRONE® (vigabatrin)? Because VIGADRONE might cause permanent vision loss, it is available to healthcare providers and patients only under a special program called the Vigabatrin Risk Evaluation and Mitigation Strategy (REMS) Program. Your healthcare provider will explain the details of this Program to you. VIGADRONE can damage the vision of anyone who takes it. Some people can have severe loss, particularly to their ability to see to the side when looking straight ahead (peripheral vision). With severe vision loss, you may only be able to see things straight in front of you (sometimes called "tunnel vision"). You may also have blurry vision. If this happens, it will not get better. Tell your healthcare provider right away if you (or your child): might not be seeing as well as before starting VIGADRONE; start to trip, bump into things, or are more clumsy than usual; are surprised by people or things coming in front of you that seem to come out of nowhere; or if your baby is acting differently than normal. These changes can mean that vision damage has occurred. Regular vision testing is recommended. It is recommended that your healthcare provider test your (or your child's) vision before or within 4 weeks after starting VIGADRONE, and at least every 3 months during treatment until VIGADRONE is stopped. It is also recommended that vision be tested about 3 to 6 months after VIGADRONE is stopped. It is difficult to test vision in babies, but to the extent possible, all patients should have their vision tested. Your healthcare provider will determine if testing can be done. Regular vision testing is important because damage can happen before any changes are noticed. Vision tests cannot prevent the vision damage that can happen with VIGADRONE, but they do allow VIGADRONE to be stopped if vision has gotten worse, which usually will lessen further damage. Even these regular vision tests may not show vision damage before it is serious and permanent. Parents, caregivers, and healthcare providers may not recognize the symptoms, or find vision loss in patients, until it is severe. If you do not have these vision tests regularly, your healthcare provider may stop prescribing VIGADRONE for you (or your child). Some people are not able to complete vision testing. If vision testing cannot be done, your healthcare provider may continue prescribing VIGADRONE, but will not be able to watch for any vision loss. Magnetic resonance imaging (MRI) changes in patients with infantile spasms (IS). Brain pictures taken by MRI show changes in some patients after they are given VIGADRONE. It is not known if these changes are harmful. A type of swelling in the brain called intramyelinic edema (IME) has been seen in autopsy examination of patients treated with vigabatrin. Risk of suicidal thoughts or actions. Like other antiepileptic drugs, VIGADRONE may cause suicidal thoughts and actions in some people (about 1 in 500 people). Call a healthcare provider right away if you (or your child) have any symptoms, especially sudden changes in mood, behaviors, thoughts or feelings, and especially if they are new, worse, or worry you. Do not stop VIGADRONE without first talking to a healthcare provider. Stopping VIGADRONE suddenly can cause seizures that will not stop. VIGADRONE can cause serious side effects such as low red blood cell counts (anemia), sleepiness and tiredness, nerve problems, weight gain, and swelling. Because VIGADRONE causes sleepiness and tiredness, do not drive, operate machinery, or perform any hazardous task, unless it is decided that these things can be done safely. VIGADRONE may make certain types of seizures worse. Tell your healthcare provider right away if seizures get worse. Before starting VIGADRONE, tell your doctor about all of your (or your child's) medical conditions including depression, mood problems, suicidal thoughts or behavior, any allergic reaction to VIGADRONE, vision problems, kidney problems, low red blood cell counts (anemia), and any nervous or mental illnesses. Tell your doctor about all the medicines you (or your child) take. If you are breastfeeding or plan to breastfeed, VIGADRONE can pass into breast milk and may harm your baby. Breastfeeding is not recommended. If you are pregnant or plan to become pregnant, VIGADRONE can cause harm to your unborn baby. You and your healthcare provider will have to decide if you should take VIGADRONE while you are pregnant. The most common side effects of VIGADRONE in adults include: blurred vision, sleepiness, dizziness, problems walking or feeling uncoordinated, shaking (tremor) and tiredness. The most common side effect of VIGADRONE in children 3 to 16 years of age is weight gain. Also expect side effects like those seen in adults. The most common side effects of VIGADRONE in babies include: sleepiness (sleepy babies may have a harder time suckling and feeding or may be irritable), swelling in the bronchial tubes (bronchitis), ear infection and irritability. Tell your healthcare provider if you or your child have any side effect that bothers you or that does not go away. This is the most important information to know about VIGADRONE, but it is not all the safety information. For more information, ask your healthcare provider or pharmacist, or please see the VIGADRONE Medication Guide, full Prescribing Information including Boxed Warning for risk of permanent vision loss, and Instructions for Use. You can also visit VIGADRONE.com, upsher-smith.com or call 1-888-650-3789. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-332-1088. WHAT IS VIGADRONE? VIGADRONE® (vigabatrin) is a prescription medicine used to treat: Infantile Spasms (IS) in patients 1 month to 2 years of age, if you and your healthcare provider decide the possible benefits of taking VIGADRONE are more important than the possible risk of vision loss. Refractory Complex Partial Seizures (CPS) in adults and children 2 years and older with refractory complex partial seizures (CPS) along with other treatments if: The CPS do not respond well enough to several other treatments, and You and your healthcare provider decide the possible benefit of taking VIGADRONE is more important than the risk of vision loss. VIGADRONE should not be the first medicine used to treat CPS. About Upsher-Smith Upsher-Smith Laboratories, LLC, now a member of Bora Group, is a trusted U.S. pharmaceutical company that strives to improve the health and lives of patients through an unwavering commitment to high-quality products and sustainable growth. We bring generics and brands to a wide array of customers, always backed by our attentive level of service, strong industry relationships, and dedication to uninterrupted supply. For more information, visit . About Bora Founded in 2007, Bora Pharmaceutical Co., Ltd. ("Bora" or "the Company", 6472.TW) now is the largest pharmaceutical manufacturer in Taiwan with well-connected global distribution to supply more than 100 countries around the world. Bora is dedicated to becoming a global leader in pharmaceutical manufacturing by offering its clients the best quality, efficiency and reliability. For more information, visit . VIGADRONE and Promise of Support are trademarks of Upsher-Smith Laboratories, LLC. VIGAFYDE is a trademark of Pyros Pharmaceuticals, Inc. SOURCE Upsher-Smith Laboratories, LLC WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalAcquisition

02 Dec 2024

·www.globenewswire.com

Ovid Therapeutics to Present Multiple Posters Supporting Its Pipeline Programs Targeting Neuronal Hyperexcitability at the American Epilepsy Society 2024 Annual Meeting

Two preclinical studies to be presented on OV329, a potential next-generation GABA aminotransferase inhibitor, highlighting its safety profile and lack of ocular accumulation relative to vigabatrin Findings to be presented on the effects of OV329 on elevating GABA and suppressing seizures as evaluated in the lithium-pilocarpine model of status epilepticus A study of the effect of OV350, a KCC2 direct activator, in rescuing animals from nerve agent-induced benzodiazepine-resistant refractory status epilepticus to be presented NEW YORK, Dec. 02, 2024 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (Nasdaq: OVID), a biopharmaceutical company dedicated to developing medicines for brain conditions with significant unmet need, today announced it will present four posters that support the Company’s OV329 and OV350 pipeline programs for the treatment of conditions caused by neuronal hyperexcitability at the 2024 American Epilepsy Society (AES) Annual Meeting in Los Angeles, California. “We are encouraged by the results of preclinical studies comparing OV329 to vigabatrin, which further elucidate OV329’s pharmacodynamic and safety profile, including its lack of accumulation in the brain, retina, and eye,” said Zhong Zhong, Ph.D., Chief Scientific Officer of Ovid Therapeutics. “These findings, alongside preclinical studies demonstrating rapid exposure in the brain, further support OV329’s potential to be a best-in-class GABA-aminotransferase (GABA-AT) inhibitor. GABA-AT inhibition is a proven mechanism of action, yet it has had limited clinical use over the years due to reported ocular toxicities associated with the first-generation medicine. OV329 may address the therapeutic needs of patients seeking anti-convulsant efficacy and improved safety without sedation.” “Additionally, we are excited by new findings that reinforce OV350’s activity in terminating seizures and providing neuroprotective benefits in animals. OV350 is the first of multiple programs we are developing that directly activate the potassium chloride co-transporter 2 (KCC2), a fundamental target in restoring inhibitory/excitatory balance. Next year, we hope to be the first company to study a KCC2 direct activator in humans.” POSTERS TO BE PRESENTED ON OVID DEVELOPMENT PROGRAMS: OV329: A Potential Next-Generation GABA-AT Inhibitor Title: OV329 A Potent GABA-AT Inhibitor Does Not Accumulate in Mouse Retina: A Pharmacokinetic Study to Differentiate Eye Accumulation Between VigabatrinSession Date & Time: 12:00-1:45 p.m. PST, Monday, December 9Presenter: Zhong Zhong, Ph. D. Poster Number: # 3.062 Title: OV329 Rapidly Inhibits GABA-AT, Elevates Brain GABA Levels and Leads to Seizure Suppression Following IV Administration in the Rat Lithium-Pilocarpine Model of Status Epilepticus Session Date & Time: 12:00-2:00 p.m. PST, Saturday, December 7Presenter: Julia Tsai, Ph.D. Poster Number: # 1.475 Title: Comparing the Effects of OV329 and Vigabatrin on GABA-AT Activity, and the Efficacy of Phasic And Tonic InhibitionSession Date & Time: 12:00-2:00 p.m. PST, Sunday, December 8Presenter: Philip Colmers Ph.D. Poster Number: # 2.353 OV350: A KCC2 Direct Activator Title: Evaluation of Anticonvulsant Efficacy of the KCC2 Activator, OV350, in a Rat Model of Nerve Agent PoisoningSession Date: 12:00-2:00 p.m. PST, Saturday, December 7Presenter: Toshiya Nishi, DVMPoster Number: # 1.477 About Ovid Therapeutics Ovid Therapeutics Inc. is a New York-based biopharmaceutical company dedicated to developing medicines for brain conditions with significant unmet need. 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 multiple neurological and neuropsychiatric disorders. Ovid is developing: OV329, a next-generation GABA-aminotransferase inhibitor, as a potential therapy for treatment-resistant seizures and other undisclosed indications; OV350, and a library of compounds that directly activate the KCC2 transporter, for multiple CNS disorders; and OV888/GV101, a highly selective ROCK2 inhibitor, for undisclosed neurovascular and neuro-inflammatory conditions. 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 OV329, OV350 and other compounds from Ovid’s library of direct activators of KCC2, and OV888/GV101; the potential therapeutic opportunity of OV329, OV350 and other compounds from Ovid’s library of direct activators of KCC2, and OV888/GV101; OV329’s potential to be a best-in-class GABA-aminotransferase (GABA-AT) inhibitor; the expected timing of initiation of Ovid’s clinical studies; and other statements that are not historical fact. You can identify forward-looking statements because they contain words such as “anticipates,” “believes,” “expects,” “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, impediments to Ovid’s ability to achieve expected benefits of cost-savings efforts, 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 most recently filed Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”), and in subsequent and 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. ContactsInvestor RelationsGarret BonneyIR@ovidrx.com MediaRaquel CaboRCabo@ovidrx.com

Clinical Study

12 Nov 2024

·www.globenewswire.com

Ovid Therapeutics Reports Business Updates and Third Quarter 2024 Financial Results

A Phase 1 SAD/MAD study of OV329 is progressing as planned, and based on encouraging human safety data to date, Ovid will engage regulators about adding cohorts to increase potential dosing opportunities for Phase 2 programs.A regulatory application for a Phase 1 trial of OV350, the first candidate from Ovid's KCC2 direct activator library, is expected to be filed in Q4 2024.The Company will host a KCC2 Download Day on November 13 to provide updates on Ovid's platform of KCC2 direct activators and their broad therapeutic potential.Ovid and Graviton are pausing the initiation of a Phase 2 study of OV888/GV101 to evaluate emerging insights from two recently completed competitor trials in cerebral cavernous malformations.Cash and marketable securities of $62.7 million as of September 30, 2024, is expected to support operations and development programs into H2 2026. NEW YORK, Nov. 12, 2024 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (Nasdaq: OVID), a biopharmaceutical company dedicated to developing medicines for brain conditions with significant unmet need, today reported business updates and financial results for the third quarter ended September 30, 2024. "The biopharmaceutical industry is entering an exciting new era of neurotherapeutics, and we are poised to address significant unmet needs in diseases of the central nervous system. Our innovative programs featuring differentiated mechanisms of action, such as GABA-aminotransferase inhibition, KCC2 direct activation, and ROCK2 inhibition, offer powerful approaches to address fundamental biological causes of neurological and neuropsychiatric conditions and symptoms," said Dr. Jeremy Levin, D.Phil., MB BChir., Chairman and CEO of Ovid Therapeutics. "With a clear and disciplined capital strategy, we're channeling our resources toward programs that we believe have the greatest potential to deliver meaningful clinical outcomes and pivotal milestones within our financial runway. This includes the proactive decision to pause the initiation of the Phase 2 program in CCM to incorporate fresh insights from recent competitor trials in an effort to strengthen the approach for this community." General Corporate & Business Updates Pipeline strategy and focus: Ovid is advancing its pipeline in a fiscally disciplined and clinically and scientifically rigorous fashion in an effort to achieve its vision of becoming a leader in neurotherapeutics for brain disorders with significant unmet need. Central to the Company's strategy is identifying and developing differentiated mechanisms of action to interdict unaddressed biological targets in the brain that are fundamental to disease pathology. This strategy includes achieving a potential best-in-class next generation GABA aminotransferase inhibitor, (GABA-AT) translating the direct activation of the potassium chloride co-transporter 2 (KCC2) for a broad range of central nervous system (CNS) conditions, and pioneering Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibition for neurovascular and neuro-inflammatory conditions.Capital allocation and business development strategy: Over the last quarter, Ovid has streamlined its operations, prioritized its pipeline programs and aligned its financial strategy to support the potential achievement of key value-creating clinical milestones. This includes a focus on advancing the development of OV329 and Ovid's library of KCC2 direct activators. Ovid expects its cash runway to support operations and clinical development into H2 2026. During this period, Ovid plans to achieve multiple clinical and regulatory milestones associated with its OV329 and OV350 programs, and to advance undisclosed ROCK2 inhibition programs with its collaborator, Graviton Bioscience. Ovid will continue to explore partnerships and co-development opportunities for select programs to accelerate development and offset costs.Strengthened leadership team: In the third quarter of 2024, Ovid strengthened its leadership team in capabilities central to the execution of its corporate strategy and vision. This included the promotion of Meg Alexander to President and Chief Operating Officer and the hiring of Dr. Amanda Banks to serve as Chief Development Officer. Collectively, the executive team will focus on the progression of Ovid's pipeline as well as corporate and business development. OV329 A next-generation GABA aminotransferase inhibitor: Ovid is developing OV329 as a next-generation GABA-AT inhibitor that seeks to reduce neuronal hyperexcitability with less sedation and without ocular changes that are associated with an older drug in the class, vigabatrin. Ovid's preclinical characterization suggests that OV329 is more potent, delivers synaptic and extra-synaptic inhibition, and has a lasting pharmacodynamic effect with rapid tissue clearance.Phase 1: Ovid is executing, as planned, a Phase 1 multiple ascending dose (MAD) study evaluating OV329. Based upon supportive human safety data to date, Ovid plans to explore with regulators adding cohorts to increase dosing opportunities for future Phase 2 programs. Topline data are anticipated in 2025, and Ovid will provide more detailed timelines following discussions with regulators. The Company anticipates sharing results on safety, tolerability, and two biomarkers that may provide a signal for target engagement and clinical effect, using magnetic resonance spectrometry and transcranial magnetic spectroscopy, respectively. Ocular safety characterization: To evaluate OV329's safety compared to vigabatrin, Ovid has conducted additional animal experiments to evaluate the risk of drug accumulating in the eye and causing retinal cell dysregulation. At the Epilepsy Pipeline Conference in September 2024, Ovid presented results from an animal study demonstrating that OV329 did not accumulate in animal eyes in contrast with vigabatrin. OV329 was present in the brain plasma of mice and then rapidly cleared the tissue and remained undetectable in the retina, eye, and brain. In contrast, vigabatrin was demonstrated to accumulate in the eye, retina and brain, which is consistent with previously published independent research. The full results from this head-to-head study will be presented at the 2024 American Epilepsy Society conference in December. OV350 and KCC2 library OV350 Phase 1, first-in-human study for a KCC2 direct activator: Ovid expects to submit a regulatory application for a Phase 1 trial of OV350 before year end 2024, and to initiate the first-in-human study for this class of molecule in Q1 2025. OV350 is the first of multiple anticipated programs from Ovid's library of KCC2 direct activators. The Phase 1 trial intends to evaluate the safety, tolerability and pharmacokinetic parameters of an IV formulation of OV350 in healthy human volunteers. In preclinical and animal disease models, OV350 has demonstrated anti-psychotic and anticonvulsant effects, indicating it may have broad therapeutic utility.KCC2 direct activator library: Ovid is also progressing its KCC2 library, which comprises multiple compounds with different pharmacology and combinations of effects across neurological conditions with high unmet need, including: neuropsychiatric, neurodevelopmental and neurodegenerative applications. These compounds have unique therapeutic characteristics and are amenable for oral and intramuscular formulations to address indications across the care continuum.KCC2 Download Day: Ovid will be hosting a session on November 13, 2024, from 9:30-11:30 AM, Eastern time, focused on the therapeutic potential of its portfolio of KCC2 direct activators, a target fundamental to restoring neuronal homeostasis. Ovid management and recognized thought leaders will present. A live webcast of the presentation can be accessed through the Events and Presentations section of Ovid's website at https://investors.ovidrx.com. OV888/GV101 & ROCK2 inhibitor programs OV888/GV101 Capsule for CCM: Following the recent completion of long-duration competitor trials in CCM, and after discussions with key stakeholders, Ovid and Graviton Bioscience have decided to pause the initiation of the Phase 2 proof-of-concept study of OV888/GV101 capsule in CCM. Ovid and Graviton Bioscience received regulatory clearance to initiate a Phase 2 program in Israel and were in the process of applying for clearance in other regions, but they will take a strategic pause to evaluate clinical design learnings emerging from competitor Phase 2 programs. The companies are confident in the potential therapeutic effects of ROCK2 inhibition for CCM and will seek to optimize future development approaches with the benefit of further insights on study duration, enrichment strategies, endpoints, and time-to-event measurements.ROCK2 inhibition programs: Ovid and Graviton continue to pursue additional formulations of OV888/ GV101 for undisclosed cerebral vascular conditions with high unmet need. Third Quarter 2024 Financial Results Cash, cash equivalents and marketable securities as of September 30, 2024, totaled $62.7 million.Revenues from royalty agreements were $173,000 for the third quarter ended September 30, 2024, as compared to $109,000 in the same period in 2023.Research and development expenses were $7.9 million for the third quarter ended September 30, 2024, compared to $5.3 million in the same period in 2023. The increase is related to the advancement of Ovid's clinical and preclinical pipeline programs as described above.General and administrative expenses were $5.5 million for the third quarter ended September 30, 2024, as compared to $6.8 million for the same period in 2023. The decrease was driven by the previous organizational restructuring and related cost-reduction efforts.Total operating expenses were $13.4 million for the third quarter ended September 30, 2024, as compared to $12.1 million for the same period last year.Ovid reported a net loss of $14.0 million, or basic and diluted net loss per share attributable to common stockholders of $0.20, for the third quarter of 2024, as compared to a net loss of $11.3 million, or basic and diluted net loss per share attributable to common stockholders of $0.16, for the same period in 2023. About Ovid Therapeutics Ovid Therapeutics Inc. is a New York-based biopharmaceutical company dedicated to developing medicines for brain conditions with significant unmet need. 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 multiple neurological and neuropsychiatric disorders. Ovid is developing: OV329, a next-generation GABA-AT inhibitor, as a potential therapy for treatment-resistant seizures and other undisclosed indications; OV350, and a library of compounds that directly activate the KCC2 co-transporter, for multiple CNS disorders; and OV888/GV101, a highly selective ROCK2 inhibitor for undisclosed neurovascular and neuro-inflammatory conditions. 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 expected timing of initiation, completion, and results and data of Ovid’s clinical studies; the potential to add cohorts to the Phase 1 SAD/MAD study of OV329, expected timing of completion of the study and expected timing of data presentation; the expected timing of submission of a regulatory application for a Phase 1 trial of OV350 IV and the expected timing of initiation of the trial; Ovid’s evaluation of the results of two recently completed competitor trials to OV888/GV101 for CCM; Ovid’s ability to achieve expected benefits of cost-savings efforts; Ovid’s expectations regarding the duration of its cash runway and the expectation that it will support Ovid's operations and development programs; the potential use and development of OV329, OV350 and other compounds from Ovid’s library of direct activators of KCC2, and OV888/GV101; the potential therapeutic opportunity of OV329, OV350 and other compounds from Ovid’s library of direct activators of KCC2, and OV888/GV101; Ovid’s potential future business development opportunities; and other statements that are not historical fact. You can identify forward-looking statements because they contain words such as “anticipates,” “believes,” “expects,” “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, impediments to Ovid’s ability to achieve expected benefits of cost-savings efforts, 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 most recently filed Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”), and in subsequent and 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 Three Months EndedSeptember 30, 2024 For The Three Months EndedSeptember 30, 2023Revenue: License and other revenue$173 $109 Total revenue 173 109 Operating expenses: Research and development 7,855 5,333 General and administrative 5,544 6,805 Total operating expenses 13,399 12,138 Loss from operations (13,226) (12,029)Other income (expense), net (780) 776 Loss before provision for income taxes (14,006) (11,253)Provision for income taxes — — Net loss$(14,006) $(11,253)Net loss per share, basic$(0.20) $(0.16)Net loss per share, diluted$(0.20) $(0.16)Weighted-average common shares outstanding, basic 70,975,778 70,618,609 Weighted-average common shares outstanding, diluted 70,975,778 70,618,609 Select Condensed Consolidated Balance Sheet DataUnaudited (in thousands)September 30, 2024 December 31, 2023Cash, cash equivalents and marketable securities$62,712 $105,834 Working capital(1) 54,197 98,125 Total assets 102,654 144,027 Total stockholders’ equity 76,290 87,797 (1)Working capital defined as current assets less current liabilities Contacts Investor RelationsGarret BonneyIR@ovidrx.com MediaRaquel CaboRCabo@ovidrx.com

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KEGG	Wiki	ATC	Drug Bank
D00535	Vigabatrin	N03AG04	DB01080

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Indication	Country/Location	Organization	Date
Seizures	US	Lundbeck Pharmaceuticals Ltd.	21 Aug 2009
Spasms, Infantile	US	Lundbeck Pharmaceuticals Ltd.	21 Aug 2009
Epilepsy	MX	Lundbeck LLC	05 Apr 2004

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Indication	Highest Phase	Country/Location	Organization	Date
Tuberous Sclerosis	Preclinical	US	Pyros Pharmaceuticals, Inc.Startup	02 Nov 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


FDA_CDER Manual	Not Applicable	Spasms, Infantile	40	vigabatrin	ahuuwqszqr(wfxakktlyd) = gsskzlbtsq isxmbhvxby (xktglekrfq ) View more	Positive	17 Jun 2024
FDA_CDER Manual	Not Applicable	Spasms, Infantile	40	placebo	ahuuwqszqr(wfxakktlyd) = syufheceaq isxmbhvxby (xktglekrfq )	Positive	17 Jun 2024
FDA_CDER Manual	Not Applicable	Spasms, Infantile	221	Vigabatrin (18-36 mg/kg/day)	xopnzulhlg(zzbxfyktyz) = vdwffqvfua yfowoqgzyx (ditmbjalvw )	Positive	17 Jun 2024
FDA_CDER Manual	Not Applicable	Spasms, Infantile	221	Vigabatrin (100-148 mg/kg/day)	xopnzulhlg(zzbxfyktyz) = nnanljdhef yfowoqgzyx (ditmbjalvw )	Positive	17 Jun 2024
IEC2023	Not Applicable	-	-	Antiseizure medication (ASM) exposed pregnant people without epilepsy (PPWOE)	tsdsricjfx(yllddqdklj) = wjgirtkrkv csjqfrzgho (awwjbyrbaz, 1.47 - 1.76) View more	-	04 Sep 2023
NCT01585207 (CTgov)	Phase 1/2	Tourette Syndrome	4	vigabatrin	orlovjxwmf(wbuxhqamtj) = aztmnhszhf hphebihjql (yprrtzhdns, yzaisgkvgp - fnxpykzhkp) View more	-	19 Jan 2018
IEC2017	Not Applicable	Spasms, Infantile \| Tuberous Sclerosis	-	Vigabatrin (VGB)	ihtjeywnrc(twxfityzdg) = zmuxwnzmwu kplixrnpbr (yldhidudoa ) View more	-	03 Sep 2017
NCT01266291 (STARS, CTgov)	Phase 4	Seizures \| Epilepsy, Complex Partial \| Tuberous Sclerosis	1	vigabatrin	vnsijwuaif(bpawztahvu) = iktfnetnyd hgatdoewsf (uxvfibrhki, rtiujmtbfk - vthbfkhjbu) View more	-	12 Jul 2017
NCT01278173 (CTgov)	Phase 4	Seizures	65	Sabril	djtwlpfsik(qyvzhnooak) = rzwcgpshbq kwxjxztasy (sqcdjarion, umkgaqarxc - nzzpdqmeur) View more	-	07 Jun 2016
NCT01281202 (CTgov)	Phase 2/3	Cocaine-Related Disorders	207	Vigabatrin (CPP-109 Vigabatrin Tablets)	aeyjajbvgc(mjzalczbuq) = hstvrprkmr muavnqfkzh (ceuqkduwny, evcqevzucs - drtywwpcgp) View more	-	23 Feb 2016
NCT01281202 (CTgov)	Phase 2/3	Cocaine-Related Disorders	207	Matching Placebo (Placebo)	pndhmsdrtm(celcndvtdr) = wshhxcwhjh ttsbbshjqk (yfqhquxern, oslvnaghbo - lthjkhabpy) View more	-	23 Feb 2016
CNS2015	Not Applicable	Epilepsy	103	Vigabatrin	cpywtlymny(xwxkpgsbho) = few side effects and mild visual field effects in patients ufuqfqiyup (zzobpfaxop ) View more	-	25 Sep 2015
NCT01335867 (VGB, CTgov)	Phase 2	Cocaine-Related Disorders \| Alcoholism	32	Vigabatrin (Vigabatrin)	xuagbknvcz(yoqoeougzz) = klzzjzhtbc yfiigzxvdg (fkasxitbob, ksdblkiatw - bdbtnlqpom) View more	-	12 Jun 2015
NCT01335867 (VGB, CTgov)	Phase 2	Cocaine-Related Disorders \| Alcoholism	32	Placebo (Placebo)	xuagbknvcz(yoqoeougzz) = opydadbuvi yfiigzxvdg (fkasxitbob, pbimzyurce - pozyceuhqe) View more	-	12 Jun 2015

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