FDA Pauses New Enrollment in Biohaven’s Opakalim Epilepsy Program Over Rodent Metabolite Finding

The FDA has placed a partial clinical hold on new enrollment in Biohaven’s opakalim (BHV-7000) program after nonclinical testing identified a metabolite that cannot yet be adequately assessed for human risk. Existing participants can continue dosing, while the fully enrolled and randomized RISE3 pivotal study remains on track for a second-half 2026 topline readout.

FDA Hold Follows Nonclinical Metabolite Finding

The FDA issued the partial clinical hold on September 4, 2026, instructing Biohaven to pause new patient enrollment while additional nonclinical studies characterize a specific metabolite observed during rodent testing. The hold applies only to new enrollment. More than 600 patients already randomized across the BHV-7000 program can continue dosing.

The filing does not identify a confirmed clinical safety signal in humans. Biohaven said there is currently insufficient information to assess the metabolite’s risk to human subjects, and the significance of the finding remains uncertain. The company noted that the finding could be specific to rodents and not relevant to human safety. Additional nonclinical studies are expected to clarify its significance.

Opakalim Targets Refractory Focal Epilepsy

Opakalim is being developed through Biohaven’s Kv7 ion channel platform for refractory focal epilepsy. The company completed an FDA End-of-Phase 2 meeting in January 2024 and subsequently advanced the program into pivotal Phase 2/3 studies.

The two pivotal trials, BHV7000-302 (RISE2) and BHV7000-303 (RISE3), are randomized, double-blind, placebo-controlled studies evaluating adults with focal epilepsy. Their primary endpoint is the change from baseline in 28-day average seizure frequency. RISE3 evaluates 50 mg and 75 mg doses, while an associated open-label extension study, BHV7000-201, continues to provide longer-term dosing and safety follow-up.

RISE3 Enrollment Was Already Complete

The FDA action does not require RISE3 to recruit additional patients because the study was already fully enrolled and randomized. Biohaven reported that enrollment in RISE3 was completed in June 2026, with dosing continuing and topline results still expected in the second half of the year.

The September filing confirms that RISE3 is fully enrolled and randomized. Dosing therefore continues without requiring further recruitment, and Biohaven said the study’s topline data remain on track for the second half of 2026.

The situation differs for RISE2 (BHV7000-302). Existing participants can continue dosing, but new enrollment is paused while the additional nonclinical studies further characterize the metabolite. The open-label extension study also continues dosing. Biohaven said it voluntarily instituted the same plan at its global sites outside the United States.

Human Safety Relevance Remains Unresolved

More than 1,200 participants have received BHV-7000 across the development program, and Biohaven has characterized the clinical safety profile as generally safe and well tolerated to date. The current FDA action stems from a nonclinical finding involving a metabolite observed in rodent testing, rather than a reported metabolite-related adverse-event signal in clinical participants.

That distinction is important when interpreting the partial hold. The FDA is requiring additional evidence before permitting further enrollment, but the disclosed information does not establish that the metabolite causes toxicity in humans. The additional studies will determine whether the rodent finding has meaningful relevance to human safety.

SK Biopharmaceuticals Received the Relevant Data

The regulatory development follows Biohaven’s August 26, 2026, licensing agreement with SK Biopharmaceuticals. Under the agreement, SKBP will receive an exclusive, royalty-bearing worldwide license to Biohaven’s Kv7 platform, including BHV-7000 and other covered Kv7 compounds and products.

Biohaven said that all clinical and nonclinical data, including information related to metabolite characterization submitted to global regulatory authorities, had been fully disclosed to SKBP before the licensing agreement was signed. Biohaven and SKBP are continuing work on the required Hart-Scott-Rodino filing needed to close the transaction.

RISE3 Readout Remains on Track

Because RISE3 was fully enrolled and randomized before the partial clinical hold, the enrollment pause does not currently affect ongoing dosing in that study. Biohaven continues to expect topline results in the second half of 2026.

The timeline, however, is not guaranteed beyond the company’s current guidance. Additional nonclinical characterization could influence subsequent regulatory decisions and the broader development path, particularly for RISE2, where new enrollment remains paused.

For now, Biohaven’s immediate priority is to resolve the metabolite finding while completing dosing in already randomized participants. The next key catalyst is the additional nonclinical data expected in the coming weeks, followed by the planned RISE3 topline readout later in 2026.

Reference

Form 8-K for Biohaven LTD filed 09/10/2026, Biohaven, 10 September 2026