FDA Places Partial Clinical Hold on Biohaven's Epilepsy Candidate Opakalim, Pausing New Enrollment in Pivotal Program
核心洞察
The FDA issued a partial clinical hold on Biohaven's opakalim (搜索) (BHV-7000) after nonclinical rodent studies flagged a metabolite with uncertain relevance to human safety.
New patient enrollment is paused across the focal epilepsy (搜索) program, though dosing continues for more than 600 already-randomized patients, including the fully enrolled RISE-3 study.
Biohaven expects RISE-3 topline data in the second half of 2026, with the hold not affecting that timeline, while enrollment resumption timing remains uncertain.
The U.S. Food and Drug Administration has placed a partial clinical hold on the pivotal development program for Biohaven Ltd. (搜索)'s opakalim (搜索) (BHV-7000), a selective Kv7.2/7.3 potassium channel (搜索) activator in development for refractory focal epilepsy (搜索), after nonclinical rodent studies identified a drug-related metabolite for which the company said there was "insufficient information" regarding risk to humans.
According to an 8-K filed with the SEC on September 9, 2026, the FDA issued the partial clinical hold letter on September 4, pausing new patient enrollment pending results of additional nonclinical studies characterizing the metabolite. Dosing continues for all patients already randomized across the program, more than 600 in total. Biohaven said it voluntarily applied equivalent enrollment restrictions to its global sites outside the United States.
Impact on the Pivotal Program
The hold affects the two pivotal trials in refractory focal epilepsy (搜索) differently. BHV7000-303 (RISE-3, NCT06309966) was fully enrolled and randomized before the hold was issued, and its topline data timeline is unaffected; Biohaven continues to expect a readout in the second half of 2026. The companion pivotal study, BHV7000-302 (RISE-2, NCT06132893), which has an 8-week double-blind treatment period, continues dosing but cannot enroll new patients. The open-label extension study (BHV7000-201, NCT06443463) also continues dosing.
Biohaven said the metabolite was identified during routine nonclinical characterization and that the significance of the rodent findings to human safety is uncertain and may be species-specific. The company expects the additional nonclinical studies to generate clarifying data within weeks, though the timing of enrollment resumption remains uncertain.
Licensing Deal With SK Biopharmaceuticals
The regulatory action arrives days after Biohaven agreed to license the Kv7 platform to South Korea-based SK Biopharmaceuticals (搜索) in a deal worth up to $795 million overall, including an immediate $350 million upfront payment. The agreement was signed on August 26, 2026. Biohaven said it fully disclosed all clinical and nonclinical data, including the metabolite findings, to SK before the deal was signed, and the companies continue to work toward closing, when the $350 million becomes payable.
William Blair analyst Myles Minter wrote that the disclosure suggests SK "was comfortable with any issues" regarding the metabolite flagged by the FDA, and described the licensing decision as "prudent but necessary." Should opakalim (搜索) succeed in testing and win approval, Biohaven will be eligible for milestone payments and sales royalties from SK. SK already has an existing U.S. epilepsy infrastructure built around its Xcopri (cenobamate) franchise.
Mechanism and Prior Setbacks
Opakalim (搜索) activates Kv7.2/7.3 heteromeric potassium channels, reducing neuronal excitability through the M-current — a mechanism distinct from GABA receptor modulation, which the company attributes to the drug's reported low rates of somnolence and dizziness in clinical studies. More than 1,200 participants have been dosed across the development program to date. The candidate previously fell short in pivotal studies in both bipolar disorder (搜索) and major depressive disorder (搜索) in 2025, and Biohaven nonetheless views it as a next-generation, selective treatment for focal epilepsy (搜索) with potential promise in pain.
The hold marks another setback for Biohaven, the second iteration of a company that sold itself to Pfizer in 2022, after which the same management team spun out a new entity with the same name. That journey has included a controversial regulatory rejection of a rare disease drug, a failed trial in spinal muscular atrophy (搜索), and a shortfall in depression. The company has restructured, cut research and development costs and changed scientific leadership, while its cash reserves have dwindled.
Competitive Landscape
Xenon Pharmaceuticals' azetukalner, also a Kv7.2/7.3 opener in Phase III for focal onset seizures, has reported positive topline data from its X-TOLE2 study and indicated plans to submit a new drug application to the FDA in the third quarter of 2026 — potentially making it the first therapy from this drug class to reach the focal epilepsy (搜索) market. A range of anti-seizure medications is already available. GlobalData, parent company of Clinical Trials Arena, forecasts the market across the seven major markets (the U.S., France, Germany, Italy, Spain, the UK and Japan) will be worth $17.8 billion in 2035.