Small Molecule · BHV-7000
Opakalim (BHV-7000)
Oral, selective activator (opener) of Kv7.2/Kv7.3 (KCNQ2/KCNQ3) voltage-gated potassium channels — the M-current — without GABA-A activity. From Biohaven; developed across epilepsy and mood. The mood programs failed (MDD POC and bipolar mania) and Biohaven deprioritized psychiatry in 2026.
- Modality
- Small molecule
- Chemical class
- benzimidazole, carboxamide
- Chemistry
- Achiral
- Mechanism
- Kv7.2 activator
- Highest phase
- Phase 3
- Lead indication
- Epilepsy
- Developer
- Biohaven Ltd. (BHVN)
- Trials
- 5 tracked · 2 recruiting · 501 sites
- Next catalyst
- 2025-03-03 — Topline data (Bipolar disorder)
Mechanism of action
Selective Kv7.2/Kv7.3 (KCNQ2/3) potassium-channel opener; EC50 ~0.6 µM for the heteromer, no GABA-A or cardiac channel activity (unlike retigabine).
| Target | Action | Affinity |
|---|---|---|
| Kv7.2primaryKCNQ2 | Activator | EC50 0.6 µMⓘ |
| Kv7.3KCNQ3 | Activator | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| BHV-7000 once-daily extended-release (oral)extended-release Once-daily extended-release oral formulation; doses up to 75 mg daily evaluated in Phase 2/3 (Phase 1 demonstrated safety/tolerability up to 120 mg daily for 15 days) | Oral | Once daily | — |
Development timeline
- Phase 2 MDD study missed primary MADRS endpoint; psychiatry deprioritized.Major depressive disorder↗
- Phase 2/3 registrational acute bipolar mania study (NCT06419582) started; YMRS day-21 primary endpoint, BHV-7000 75 mg QD vs placebo, inpatient.Bipolar disorder
- Second pivotal Phase 2/3 focal-epilepsy study (NCT06309966) started.Epilepsy
- First pivotal Phase 2/3 study in refractory focal onset epilepsy (NCT06132893) started (registered as Phase 2/3).Epilepsy
- Phase 2 MDD monotherapy POC study (NCT06419608) started.Major depressive disorder
Opakalim (BHV-7000) for Epilepsy
Phase 3RecruitingEpilepsy indication →
Lead indication for BHV-7000 (opakalim), an oral selective Kv7.2/7.3 (KCNQ2/3) potassium-channel opener restoring the M-current. Two pivotal global Phase 2/3 randomized, double-blind, placebo-controlled adjunctive studies in refractory focal onset epilepsy support registration: NCT06132893 and NCT06309966 (both recruiting), with a long-term safety open-label extension (NCT06443463). Biohaven is on track for top-line results in 2H 2026 from the first of the two pivotal focal-epilepsy studies. A separate Phase 2/3 proof-of-concept in idiopathic generalized epilepsy with generalized tonic-clonic seizures (NCT06425159, SHINE) was terminated early at n=27 (sponsor decision; enrollment challenges + portfolio prioritization) but showed a ~3-fold prolongation in median time to second GTC seizure (141 vs 47 days) without formal statistics.
Readouts
- 2H 2026AnticipatedTopline dataNCT06132893
Top-line results expected from the first of two pivotal Phase 2/3 focal-epilepsy studies to support registration ↗
- 2026-05-26ReportedInterim analysisterminatedNCT06425159
IGE proof-of-concept (SHINE) terminated early; ~3-fold prolongation in median time to second GTC seizure (141 vs 47 days), no formal statistics ↗
Opakalim (BHV-7000) for Major depressive disorder
DiscontinuedDiscontinuedMajor depressive disorder indication →
Phase 2 proof-of-concept in MDD. The monotherapy study (NCT06419608, n=336) did not meet its primary MADRS endpoint (reported 24 Dec 2025); Biohaven stated no further psychiatric trials, prioritizing immunology/obesity/epilepsy. (A separate bipolar-mania Phase 2/3, NCT06419582, also missed its YMRS endpoint in Mar 2025.) Epilepsy development continues.
Opakalim (BHV-7000) for Bipolar disorder
DiscontinuedDiscontinuedBipolar disorder indication →
Phase 2/3 registrational study (NCT06419582) of BHV-7000 75 mg once daily for the acute treatment of manic episodes (with or without mixed features) in Bipolar I Disorder. Topline reported 2025-03-03 in Biohaven's Q4/FY2024 earnings release: BHV-7000 did not statistically differentiate from placebo on the primary endpoint (change in YMRS total score from baseline to Day 21). The drug was safe and well-tolerated (75 mg QD, no treatment-emergent serious adverse events). Biohaven subsequently deprioritized psychiatry, focusing on immunology, obesity, and epilepsy; no further psychiatric trials of BHV-7000 are planned.
Readouts
- 2025-03-03AnticipatedTopline dataNCT06419582
Clinical trials
NCT06425159SHINEPhase 2/3Discontinuedn=27
A Phase 2/3 Study of BHV-7000 as Adjunctive Therapy in Subjects With Idiopathic Generalized Epilepsy With Generalized Tonic-Clonic Seizures (SHINE)
terminatedprimaryMedian time to second day with a generalized tonic-clonic (GTC) seizure over 24-week double-blind period — 141 days (opakalim 75 mg QD) vs 47 days (placebo), ~3-fold prolongation
Time-to-event proof-of-concept signal favoring opakalim; study terminated early (n=27: 15 opakalim, 12 placebo) due to enrollment challenges and portfolio prioritization, so no formal statistical testing was performed. Reported 26 May 2026.
NCT06419608BHV7000-305Phase 2Completedn=336
Phase 2 Study of BHV-7000 Monotherapy in Major Depressive Disorder
missedprimaryMADRS change at Week 6 vs placebo
Did not meet primary endpoint; trends favoring BHV-7000 in more severely depressed subgroups (hypothesis-generating). Reported 24 Dec 2025.
NCT06419582Phase 2/3Completedn=274
A Phase 2/3, Multicenter, Inpatient, Placebo-Controlled, Double-blind Trial of BHV-7000 for the Acute Treatment of Manic Episodes, With or Without Mixed Features, Associated With Bipolar I Disorder
missedprimaryChange in YMRS total score from baseline to Day 21 vs placebo
BHV-7000 75 mg once daily did not statistically differentiate from placebo on the primary endpoint (change in Young Mania Rating Scale total score from baseline to Day 21). The drug was safe and well-tolerated, with no treatment-emergent serious adverse events. Topline reported 2025-03-03 in Biohaven's Q4/FY2024 earnings release.
NCT06309966Phase 2/3Recruitingn=390
A Phase 2/3 Study to Evaluate Efficacy, Safety and Tolerability of BHV-7000 in Subjects With Refractory Focal Onset Epilepsy
NCT06132893Phase 2/3Recruitingn=390
A Phase 2/3 Study to Evaluate Efficacy, Safety and Tolerability of BHV-7000 in Subjects With Refractory Focal Onset Epilepsy
Identifiers
Sources
- BHV-7000 Acute Treatment of Bipolar Mania (NCT06419582) — ClinicalTrials.gov
- BHV-7000 Phase 2 MDD (NCT06419608) — ClinicalTrials.gov
- BHV-7000 Phase 2/3 in idiopathic generalized epilepsy with GTC seizures (NCT06425159, SHINE) — terminated — ClinicalTrials.gov
- BHV-7000 Phase 2/3 in refractory focal onset epilepsy (NCT06132893) — ClinicalTrials.gov
- BHV-7000 Phase 2/3 in refractory focal onset epilepsy (NCT06309966) — ClinicalTrials.gov
- Biohaven Phase 2 MDD update (endpoint not met) — Biohaven / PR Newswire
- Biohaven Presents New Data with BHV-7000 Once-Daily Extended-Release Formulation at AES 2024 — Biohaven / PR Newswire
- Biohaven reports new epilepsy clinical data with opakalim; 2H 2026 topline guidance for first pivotal focal-epilepsy study — Biohaven / PR Newswire
- Biohaven Reports Recent Business Developments and Q4/FY2024 Financial Results (BHV-7000 bipolar mania topline; primary endpoint not met) — Biohaven / PR Newswire
- Pharmacological characterization of BHV-7000 (Kv7.2/7.3) — American Epilepsy Society