opakalim (BHV-7000) / Biohaven, SK Bio - LARVOL DELTA

Next-Generation Pharmacotherapies for Unipolar Mood Disorders: A Leading Article on Phase II/III Drug Development Across Diverse Mechanisms. (PubMed, CNS Drugs) - "Following the US Food and Drug Administration (FDA) approval of esketamine and brexanolone in 2019, industry investment in therapeutics with novel mechanisms for mood and anxiety disorders has expanded, catalyzing a new wave of innovative interventions...The drug names discussed are ALTO-100, ALTO-203, ALTO-207, ALTO-300, BHV-7000, BI-1569912, BPL-003, COMP360, DT120, ELE-101, GATE-251, GH001, GM-1020, GM-2505, HLP003, MK-1942, NBI-1065845, NBI-1070770, NV-5138, PIPE-307, SEP-363856, SPT-300, VLS-01, and XEN1101. The US Clinical Trials registry (clinicaltrials.gov), MEDLINE, conference proceedings, and company communications such as press releases were consulted to obtain up-to-date trial information and reported outcomes. Overall, the therapeutic landscape shows an expanding range of clinical compounds under active development; nonetheless, persistent challenges remain, including approaches to therapeutics where functional unblinding may occur, the ways in which to..."

Journal • P2/3 data • Review • CNS Disorders • Mood Disorders • Psychiatry

SK Biopharmaceuticals's epilepsy drug candidate 'Opacalim (BHV-7000)' received a partial clinical hold from the U.S. Food and Drug Administration (FDA), and the company said it expects to submit additional nonclinical data to the FDA as early as the end of this month and to have the hold resolved in Oct.-Nov (Chosun Biz) - "The FDA requested additional data after toxic findings related to a specific metabolite were observed in rats dosed with Opacalim. As a result, new patient enrollment was temporarily suspended in the phase 2 and 3 RISE2 and RISE3 trials....SK Biopharmaceuticals said it identified the toxic findings during due diligence before the contract and, after reviews by internal researchers and external experts, concluded the likelihood of the same issue occurring in humans is low."

Preclinical • Trial suspension • Epilepsy

Biohaven…has ​entered into ‌a licensing agreement ​with ​South Korean drug ⁠maker ​SK Biopharmaceuticals for Biohaven's epilepsy drug ​platform, ​including Opakalim, for ‌up ⁠to $795 million (Reuters)

Licensing / partnership • Epilepsy

Expected Upcoming Milestones:…Selective Kv7 Ion Channel Activator (Opakalim) (PRNewswire) - "Continue two Phase 2/3 studies in focal epilepsy....Topline results from the Phase 2/3 RISE3 trial in focal epilepsy are expected during 2H 2026."

P2/3 data • Trial status • 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 | Active, not recruiting | Sponsor: Biohaven Therapeutics Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2026 ➔ Oct 2026 | Trial primary completion date: May 2026 ➔ Oct 2026

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

Biohaven…announced the completion of enrollment in RISE3, a pivotal Phase 2/3 randomized, double-blind, placebo-controlled studies evaluating its selective Kv7.2/7.3 channel activator, opakalim, for the treatment of refractory focal epilepsy (PRNewswire) - "Top-line results from the study are expected in 2H 2026....RISE3 (NCT06309966) enrolled adult participants with refractory focal onset seizures who experienced at least four seizures per month and took one to three concurrent ASMs, consistent with criteria used in other recent focal epilepsy ASM trials."

Enrollment closed • P2/3 data • Epilepsy

Potassium channel agonists emerging as treatment options for focal epilepsy: are we breaking new ground? (PubMed, Expert Opin Emerg Drugs) - "This mini-review summarizes the clinical evolution of Kv7 modulation, from the first-generation prototype ezogabine to more selective second-generation candidates. We outline the scientific rationale for targeting the M-current, review emerging clinical data for agents such as azetukalner (XEN1101) and opakalim (BHV-7000), and highlight preclinical strategies including dual-mechanism modulators and drug repurposing...Second-generation agents provide encouraging mechanistic and clinical proof-of-concept, but long-term success will depend on clear advantages in patient-centered outcomes over established ASMs. Future value is likely to lie in precision-medicine strategies for KCNQ2/3-related encephalopathies and a carefully defined role in managing neuropsychiatric comorbidities."

Journal • Review • CNS Disorders • Epilepsy • Psychiatry

Expected Upcoming Milestones:…Selective Kv7 Ion Channel Activator (Opakalim) (PRNewswire) - "Continue two Phase 2/3 studies in focal epilepsy; initial topline results for the first study expected in 2H 2026."

P2/3 data • Trial status • 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) - "The potency of both drugs for potentiating channels containing one copy of Kv7.2 G281E was lower compared to channels containing only WT Kv7.2/Kv7.3 subunits. Conclusions 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) - "Conclusions 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

BHV7000-201: Long-term Safety and Tolerability of BHV-7000 (clinicaltrials.gov) - P2 | N=660 | Enrolling by invitation | Sponsor: Biohaven Therapeutics Ltd. | N=448 ➔ 660

Enrollment change • CNS Disorders • Epilepsy

A Phase 1b Study of BHV-7000 in Participants With Inherited Erythromelalgia (clinicaltrials.gov) - P1 | N=5 | Enrolling by invitation | Sponsor: Biohaven Therapeutics Ltd. | Trial completion date: Jul 2026 ➔ Nov 2026 | Trial primary completion date: Jun 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • NAV1

Long-term Safety Study of BHV-7000 in Participants With Major Depressive Disorder (MDD) (clinicaltrials.gov) - P2 | N=233 | Completed | Sponsor: Biohaven Therapeutics Ltd. | Enrolling by invitation ➔ Completed | N=480 ➔ 233 | Trial completion date: Nov 2027 ➔ Mar 2026 | Trial primary completion date: Nov 2027 ➔ Mar 2026

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

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

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

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

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