opakalim (BHV-7000) / Biohaven - LARVOL DELTA

SHINE: A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures (clinicaltrials.gov) - P2/3 | N=27 | Terminated | Sponsor: Biohaven Therapeutics Ltd. | N=242 ➔ 27 | Trial completion date: Jul 2027 ➔ Mar 2026 | Completed ➔ Terminated | Trial primary completion date: Jul 2026 ➔ Mar 2026; Sponsor Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Epilepsy

SHINE: A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures (clinicaltrials.gov) - P2/3 | N=242 | Completed | Sponsor: Biohaven Therapeutics Ltd. | Recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

RISE 3: Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy (clinicaltrials.gov) - P2/3 | N=390 | Recruiting | Sponsor: Biohaven Therapeutics Ltd. | N=235 ➔ 390

Enrollment change • CNS Disorders • Epilepsy

BHV-7000 Responsive Neurostimulation System (RNS) Study (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Yale University | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy

Opakalim (BHV-7000) Potentiates the Activity of Kv7.2/7.3 Channels Containing a Single Copy of the Kv7.2 DEE-Causing Mutation, G281E (AAN 2026) - "Since the first-generation activator and opakalim activate Kv7.2 G281E-containing channels and the patient responded favorably to replacement of the first-generation activator with opakalim, therapeutic benefit likely arises from potentiation of both WT and Kv7.2 G281E-containing channels, underscoring the potential of opakalim for treatment of KCNQ2-DEE."

CNS Disorders • Dystonia • Epilepsy • Movement Disorders

Compassionate Use of Kv7.2/7.3 Potassium Channel Activator Opakalim (BHV-7000) in a Child with KCNQ2 Developmental and Epileptic Encephalopathy (AAN 2026) - "Opakalim demonstrated favorable tolerability and initial improvement in seizures followed by return to baseline seizure frequency, with no worsening compared to prior treatment with another potassium channel activator despite a history of severe exacerbation with multiple previous attempts to wean. He also showed improvement in alertness."

Clinical • CNS Disorders • Dystonia • Epilepsy • Movement Disorders

A Phase 1b Study of BHV-7000 in Participants With Inherited Erythromelalgia (clinicaltrials.gov) - P1 | N=5 | Enrolling by invitation | Sponsor: Biohaven Therapeutics Ltd. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • NAV1

SHINE: A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures (clinicaltrials.gov) - P2/3 | N=242 | Active, not recruiting | Sponsor: Biohaven Therapeutics Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy

Efficacy and Safety Study of BHV-7000 Monotherapy in Major Depression (clinicaltrials.gov) - P2 | N=336 | Completed | Sponsor: Biohaven Therapeutics Ltd. | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Expanding the toolkit: An update on the evolution of new therapies for Lennox-Gastaut Syndrome. (PubMed, Semin Pediatr Neurol) - "The purpose of this paper is to address three such aspects of treatment evolution for LGS: (1) To review data supporting the repurposing of existing drugs for use in LGS, specifically, perampanel and cenobamate. (2) To present recent (soticlestat), ongoing (carisbamate, bexicaserin, clemizole) and upcoming (opakalim) clinical drug trials for LGS...With the richness of recent trial development for LGS combined with the nascence of clinical trials for specific genetic epilepsies comes a new era in which treatment options for LGS will continue to expand. Increasing understanding of the underlying genetic and molecular underpinnings of LGS should enable development of unique therapies, with the continued aims of sustained, durable seizure control and additional positive impact on central nervous system outcomes and beyond."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

A Phase 1b Study of BHV-7000 in Participants With Inherited Erythromelalgia (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Biohaven Therapeutics Ltd.

New P1 trial

RISE 3: Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy (clinicaltrials.gov) - P2/3 | N=390 | Recruiting | Sponsor: Biohaven Therapeutics Ltd. | Trial primary completion date: Jan 2026 ➔ May 2026

Trial primary completion date • CNS Disorders • Epilepsy

Opakalim (BHV-7000) Potentiates the Activity of Kv7.2/Kv7.3 Channels Containing a Single Copy of the Kv7.2 DEE-Causing Mutation, G281E (AES 2025) - "Since the patient is heterozygous for Kv7.2 G218E, it is likely that the channel population is comprised of ~25% WT channels, 50% channels containing one copy of Kv7.2 G281E, and 25% channels containing two copies of Kv7.2 G281E. Since both the first-generation activator and opakalim could activate the Kv7.2 G281E-containing channels and the patient responded favorably to replacement of the first-generation activator with opakalim, it is likely that therapeutic benefit arises from potentiation of both WT and Kv7.2 G281E-containing channels and underscores the potential value of opakalim for treatment of other patients with Kv7.2 mutant-associated DEE."

Late-breaking abstract • CNS Disorders • Dystonia • Epilepsy • Movement Disorders

Compassionate Use of Kv7.2/7.3 Potassium Channel Activator Opakalim (BHV-7000) in a Child with KCNQ2 Developmental and Epileptic Encephalopathy: Early Promising Results (AES 2025) - "Opakalim demonstrates early tolerability and initial improvement in seizures followed by return to baseline seizure frequency, with no worsening compared to prior treatment with another potassium channel activator despite a history of severe exacerbation with attempts to wean. He also showed encouraging improvement in alertness. Follow-up evaluations will determine additional changes in EEG or clinical status."

Clinical • Late-breaking abstract • CNS Disorders • Dystonia • Epilepsy • Movement Disorders

BHV-7000 Responsive Neurostimulation System (RNS) Study (clinicaltrials.gov) - P1 | N=5 | Recruiting | Sponsor: Yale University | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

RISE 2: A Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy (clinicaltrials.gov) - P2/3 | N=390 | Recruiting | Sponsor: Biohaven Therapeutics Ltd. | Trial completion date: Sep 2025 ➔ Dec 2026 | Trial primary completion date: Aug 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Efficacy and Safety Study of BHV-7000 Monotherapy in Major Depression (clinicaltrials.gov) - P2 | N=300 | Active, not recruiting | Sponsor: Biohaven Therapeutics Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

RISE 3: Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy (clinicaltrials.gov) - P2/3 | N=390 | Recruiting | Sponsor: Biohaven Therapeutics Ltd. | Trial completion date: Sep 2025 ➔ Feb 2026 | Trial primary completion date: Aug 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

BHV-7000 Responsive Neurostimulation System (RNS) Study (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Yale University

New P1 trial • CNS Disorders • Epilepsy

BHV-7000 Open-Label Extension Bipolar Mania Study (clinicaltrials.gov) - P2 | N=94 | Terminated | Sponsor: Biohaven Therapeutics Ltd. | N=200 ➔ 94 | Trial completion date: Apr 2026 ➔ Apr 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Apr 2025; Business Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Efficacy and Safety Study of BHV-7000 Monotherapy in Major Depression (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Biohaven Therapeutics Ltd. | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: May 2025 ➔ Nov 2025

Monotherapy • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Biohaven Presents Data Across Innovative Neuroscience Portfolio at the 2025 American Academy of Neurology (AAN) Annual Meeting (PRNewswire) - "Biohaven Ltd....announced today that it will present 13 abstracts at the 2025 American Academy of Neurology (AAN) Annual Meeting, taking place from April 5 to April 9, 2025 in San Diego, California. The presentations highlight Biohaven's innovative neuroscience pipeline across multiple early and late-stage development programs including Kv7 ion channel modulation, extracellular protein degradation, TRPM3 antagonism, TYK2/JAK1 inhibition, and glutamate modulation."

Clinical data • Migraine • Parkinson's Disease

Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "IgG MoDE Degraders (1300/1310): BHV-1300 Phase 1 with the optimized subcutaneous formulation completing in 1H 2025. BHV-1310 completion of preclinical testing prior to anticipated FIH study initiating 1H 2025...Phase 1 with BHV-1400 and BHV-1600 expected to be completed in 1H 2025...Kv7 Activator (BHV-7000): Pivotal major depressive disorder topline results expected in 2H 2025. Focal epilepsy study topline results expected in 1H 2026."

Clinical data • Preclinical • Trial completion date • Epilepsy • IgA Nephropathy • Immunology • Major Depressive Disorder

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 (AAN 2025) - P2/3 | "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."

Clinical • P2/3 data • CNS Disorders • Epilepsy • Mental Retardation • Psychiatry

Phase 1 Multiple Ascending Dose Studies Demonstrate Favorable Safety and Tolerability of BHV-7000, a Novel Kv7 Potassium Channel Activator (AAN 2025) - "BHV-7000 was safe and well tolerated in multiple-dose Phase 1 studies across all doses evaluated for up to 15 days. Adverse events typically associated with other ASMs, such as somnolence and cognitive/mood disturbances, were not reported at equivalent doses to those currently being dosed in Phase 3 trials in focal epilepsy, generalized epilepsy, major depressive disorder, and bipolar disorder."

Clinical • P1 data • Back Pain • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Constipation • Depression • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mental Retardation • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry