Abstract Details

Title A Modern Design for a Phase 2/3 Randomized, Double-blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BHV-7000 in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-016

Objective

Describe the rationale and design of a registrational clinical trial with BHV-7000 in idiopathic generalized epilepsy (IGE) with generalized tonic-clonic (GTC) seizures.

Background

Epilepsy studies are traditionally placebo-controlled, change-from-baseline endpoint studies; participants receiving placebo for a fixed duration remain at risk for continued seizures, injury, and sudden unexpected death in epilepsy (SUDEP). We designed an innovative clinical trial that reduces these risks by utilizing a time to event (TTE) endpoint (Vossler 2020). BHV-7000 is a small molecule, selective activator of Kv7.2/7.3 potassium channels, in late-stage clinical development for epilepsy and neuropsychiatric disorders. In phase 1 studies, BHV-7000 was safe and well tolerated without CNS adverse effects typical of ASMs, such as somnolence.

Design/Methods

SHINE is a Phase 2/3 randomized, double-blind, placebo-controlled study (NCT06425159), with an open-label extension (OLE), to evaluate the efficacy and safety of BHV-7000 in people with IGE with GTC seizures. Adults aged 18-75 years receiving 1-3 ASMs are eligible. Participants must have drug resistant epilepsy defined as failure of adequate trials of 2 tolerated and appropriately chosen ASM schedules. Approximately 242 participants will be randomized 1:1 to BHV-7000 75 mg or placebo once daily and treated for up to 24 weeks.

Results

SHINE is currently ongoing. An FDA-endorsed time-to-event (TTE) primary endpoint is utilized; participants end double-blind treatment early if/when they have the protocol-defined seizure event of a second day with a GTC seizure and may enter the optional OLE phase. A key secondary endpoint is the proportion of participants with GTC seizure freedom during the double-blind phase, estimated using Kaplan-Meier methods. Safety and tolerability are also assessed.

Conclusions

SHINE is an innovative registrational study in IGE with the differentiated Kv7 activator BHV-7000. This patient-centric study utilizes a TTE endpoint that decreases time on placebo, potentially reducing the risk of exposure to additional seizures, injury, and SUDEP.

Authors/Disclosures
Jason Lerner, MD (Biohaven) PRESENTER	Dr. Lerner has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Lerner has or had stock in Biohaven Pharmaceuticals.
David Stock	David Stock has nothing to disclose.
Michael E. Bozik, MD (Biohaven Pharmaceuticals)	Dr. Bozik has received personal compensation for serving as an employee of Biohaven . Dr. Bozik has stock in Biohaven.
Vivian M. Suarez, MD (Biohaven)	Dr. Suarez has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Biohaven.
Christopher Jensen, PharmD (Biohaven Pharmaceuticals)	Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals.
Lia Donahue (Biohaven)	Lia Donahue has nothing to disclose.
Michelle DeGrosky (Biohaven)	Ms. DeGrosky has nothing to disclose.
Nick Kozauer (Biohaven Pharmaceuticals)	Dr. Kozauer has received personal compensation for serving as an employee of Biohaven. Dr. Kozauer has stock in Biohaven.
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Irfan Qureshi, MD (Biohaven Pharmaceuticals)	Dr. Qureshi has received personal compensation for serving as an employee of Biohaven. Dr. Qureshi has stock in Biohaven Pharmaceuticals.
Wesley Kerr, MD, PhD (University of Pittsburgh)	Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Lifesciences. Dr. Kerr has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Kerr has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Kerr has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurelis. Dr. Kerr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for QurAlis. Dr. Kerr has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven Pharmaceuticals. Dr. Kerr has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsia. The institution of Dr. Kerr has received research support from NINDS. The institution of Dr. Kerr has received research support from American Epilepsy Society. The institution of Dr. Kerr has received research support from ��ɫ��. The institution of Dr. Kerr has received research support from SK Life Science. The institution of Dr. Kerr has received research support from Biohaven Pharmaceuticals. Dr. Kerr has received publishing royalties from a publication relating to health care.
Jacqueline French, MD, FAAN (NYU Comprehensive Epilepsy Ctr)	Dr. French has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Epilepsy Foundation. The institution of Dr. French has received research support from Epilepsy Study Consortium/ Epilepsy Foundation (Funded by UCB). The institution of Dr. French has received research support from GW/One8 Foundation/FACES. The institution of Dr. French has received research support from NINDS. The institution of Dr. French has received research support from Xenon. The institution of Dr. French has received research support from Cerevel. The institution of Dr. French has received research support from FACES. The institution of Dr. French has received research support from UCB. The institution of Dr. French has received research support from Epilepsy Study Consortium. The institution of Dr. French has received research support from UCB. The institution of Dr. French has received research support from Praxis. Dr. French has received personal compensation in the range of $50,000-$99,999 for serving as a Chief Medical/Innovation Officer with Epilepsy Foundation. Dr. French has a non-compensated relationship as a Consultant with Acadia Pharmaceuticals Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Access Industries that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Acuta Capital Partners LLC that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with AFASCI Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Agrithera, Inc. that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Alkermes that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Alterity Therapeutics Limited that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Angelini Pharma S.p.A. that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Autifony Therapeutics Limited that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Axonis Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Bain Capital that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Beacon Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Biogen that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Biohaven Pharma that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Bloom Science, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Bright Minds Biosciences, Inc. that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Capsidia Biotherapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Cerebral Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cerecin, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Cerevel that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting, SAB with Cognizance Biomarkers that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Ceribell that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cowen that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Crossject that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory Board with EcoR1 Capital that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with EG 427 that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant, Advisory Board with Eisai that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Encoded Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant/Advisory Board with Engrail that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Epitel, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with EpiMinder that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Grin Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Harmony that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory Board with Ionis Pharmaceutical that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with iQure Pharma, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with IQVIA that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Janssen Pharma that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Jazz Pharmaceutical that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Leal Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, with Livanova that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with London Research & Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Longboard Pharmaceutical that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Maplight Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Marinus that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Medscape/Web MD that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Modulight Bio that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Montara Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Mosaica Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Neumarker that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Neumirna Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neurelis that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consulting, Advisory Board with Neurocrine that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Neuropace that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with NeuroPro Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Neuroventis that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Neurona Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting, Advisory Board with Neuvarti that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Noema that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Ono Pharmaceutical that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting, Advisory Board with Otsuka that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consulting, Advisory Board with Ovid Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Praxis that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with PureTech LYT Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with QurAlis Corp that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Rapport Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Receptor Holdings, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Rivervest Venture Partners that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Sage Therapeutics, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with SK Life Science that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Stoke that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Stream Neuroscience that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Supernus that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Takeda that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Taysha Gene Therapies that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with UCB, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with uniQure that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Ventus Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Vida Ventures Management that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Xenon Pharmaceuticals that is relevant to AAN interests or activities.

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