BHV-4157 · program
Troriluzole (BHV-4157) for Obsessive-compulsive disorder
Adjunctive troriluzole for obsessive-compulsive disorder. After a Phase 2/3 proof-of-concept (BHV4157-202 / NCT03299166) missed its Week-12 Y-BOCS primary endpoint in 2020, Biohaven advanced two replicate, better-powered adjunctive Phase 3 studies at 280 mg/day (BHV4157-302 / NCT04641143 and BHV4157-303 / NCT04693351). On 11 Aug 2025 (Q2-2025 results) Biohaven reported the Phase 3 OCD trial was completed with no efficacy signal detected and is ending OCD development to redirect resources. This was the second OCD failure for the asset. (Troriluzole remains a separate, non-OCD program in spinocerebellar ataxia, where it received an FDA Complete Response Letter on 4 Nov 2025 — not modeled in this OCD record.)
Development timeline
- missedPhase 3 OCD trial completed with no efficacy signal; Biohaven discontinues troriluzole in OCD.↗
- Replicate adjunctive Phase 3 OCD program initiated: BHV4157-302 (NCT04641143, first patient Dec 2020) and BHV4157-303 (NCT04693351, started Jan 2021), troriluzole 200 mg titrated to 280 mg/day for 10 weeks in patients with inadequate SOC response.
Readouts
Clinical trials in Obsessive-compulsive disorder
NCT04693351BHV4157-303Phase 3Completedn=589
A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder
missedprimaryY-BOCS total score change from baseline (adjunctive troriluzole 280 mg)
Replicate Phase 3 adjunctive study. Biohaven (Q2-2025, 11 Aug 2025) reported the Phase 3 OCD program showed no efficacy signal and discontinued OCD development; per-arm Y-BOCS effect size / p-value not disclosed in the company readout, so left null.
NCT04641143BHV4157-302Phase 3Completedn=456
A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder
missedprimaryY-BOCS total score change from baseline (adjunctive troriluzole 280 mg)
Replicate Phase 3 adjunctive study. Biohaven (Q2-2025, 11 Aug 2025) reported the Phase 3 OCD program showed no efficacy signal and discontinued OCD development; per-arm Y-BOCS effect size / p-value not disclosed in the company readout, so left null.
NCT03299166BHV4157-202Phase 2/3Completedn=248
A Randomized, Double-blind, Placebo-controlled Trial of Adjunctive Troriluzole in Obsessive Compulsive Disorder
metsecondaryY-BOCS total score change from baseline at Week 8 — troriluzole -5.1 vs placebo -3.6 (0.041)
Nominally significant separation at Week 8 (not the primary timepoint); cited by Biohaven as a consistent treatment-benefit signal supporting Phase 3.
missedprimaryY-BOCS total score change from baseline at Week 12 — troriluzole -5.9 vs placebo -4.9 (difference -1.0) (0.2202)
Primary Week-12 Y-BOCS endpoint not met; troriluzole showed numerical but non-significant superiority over placebo. Enrollment 426 screened / 248 randomized.
Mechanism of action
Troriluzole is a tripeptide prodrug rapidly cleaved by aminopeptidases to release riluzole, a glutamate modulator. Riluzole lowers excess synaptic glutamate by two complementary actions: inhibition of presynaptic glutamate release (associated with voltage-gated sodium-channel modulation) and upregulation of the astrocytic excitatory amino acid transporter EAAT2/GLT-1 (SLC1A2), which clears >90% of extracellular glutamate. The OCD rationale was correction of glutamatergic dysregulation in cortico-striato-thalamo-cortical circuits. No clean single-site binding constant defines this effect; affinities are left null (prodrug; multi-mechanism active moiety).
| Target | Action | Affinity |
|---|---|---|
| EAAT2primarySLC1A2 | Modulator | —ⓘ |
| Presynaptic glutamate release (voltage-gated Na+ channels) | Inhibitor | —ⓘ |
← Full BHV-4157 compound page (identity, identifiers, all indications)
Sources
- Adjunctive Troriluzole in OCD - Phase 2/3 (BHV4157-202, NCT03299166) — ClinicalTrials.gov
- Adjunctive Troriluzole in OCD - Phase 3 (BHV4157-302, NCT04641143) — ClinicalTrials.gov
- Adjunctive Troriluzole in OCD - Phase 3 (BHV4157-303, NCT04693351) — ClinicalTrials.gov
- Biohaven Announces OCD Proof of Concept Phase 2/3 Study Results and Program Update — Biohaven / PR Newswire
- Biohaven reports Q2-2025 financial results and recent business developments (Phase 3 OCD trial completed with no efficacy signal; OCD program ended) - 11 Aug 2025 — Biohaven Ltd. / IR
- Riluzole - ligand page (active moiety of troriluzole) — IUPHAR/BPS Guide to Pharmacology
- Riluzole elevates GLT-1 (EAAT2/SLC1A2) activity and levels in striatal astrocytes — Neurochem Int (PMC)