The US Food and Drug Administration (FDA) has placed a partial clinical hold on the pivotal trials evaluating Biohaven’s epilepsy candidate, opakalim, following safety signals found during comprehensive metabolite characterisation in the company’s nonclinical testing.
In an 8-K form, Biohaven detailed its communications with global regulators, in which the company shared that there was “insufficient information” around the risk of a specific opakalim metabolite to humans, which was identified through nonclinical rodent-based testing.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
Following this update, the FDA placed a partial clinical hold on the pivotal programme evaluating opakalim in focal epilepsy, while also instructing Biohaven to pause new enrolment until conclusive nonclinical data on the metabolite is generated.
While the Connecticut-based pharma will no longer be able to enrol new patients to the programme, it does have the greenlight to continue dosing existing patients for the two pivotal trials, RISE-2 (NCT06132893) and RISE-3 (NCT06309966), as well as the open-label extension study (NCT06443463). Thus, the partial clinical hold will only have a notable impact on RISE-2, as RISE-3 has already fully enrolled and randomised.
Biohaven does not expect this partial clinical hold to have an impact on the timeline for RISE-3, with the company expecting a readout in the second half of 2026.
This clinical hold comes just days after SK Biopharmaceuticals bought the global rights to opakalim, also known as BHV-7000, from Biohaven for $350m upfront. The licensor notes that SK had received access to all the clinical and nonclinical data – including the metabolite characterisation – before the agreement was signed.
The developmental pause marks another setback for opakalim, which previously failed pivotal studies in both bipolar disorder and major depressive disorder (MDD) in 2025.
Azetukalner and opakalim’s race to the focal epilepsy market
Biohaven designed opakalim as a selective opener of the voltage-gated potassium channels known as Kv7.2 and 7.3, which are responsible for the control of cell excitability in the nervous system.
However, the company is not the only one to explore the anti-seizure potential of this mechanism, as Xenon Pharmaceuticals is also progressing its rival drug, azetukalner, in focal epilepsy.
Following the drug’s late-stage success, Xenon plans to submit a New Drug Application (NDA) to the FDA for azetukalner in Q3 2026 – meaning it could become the first therapy from this drug class to secure a place on the focal epilepsy market. There are, however, a range of anti-seizure medications already available.
If either azetukalner or opakalim were to gain approval, they will enter a market that GlobalData, parent company of Clinical Trials Arena, forecasts will be worth $17.8bn in 2035 across the seven major markets (7MM: the US, France, Germany, Italy, Spain, the UK and Japan).
