FDA Partial Clinical Hold Halts New Enrollment in SK Biopharmaceuticals' Opacalim RISE2 Epilepsy Trial
核心洞察
The FDA placed a partial clinical hold on opacalim (搜索) (BHV-7000), the epilepsy candidate SK Biopharmaceuticals (搜索) in-licensed from Biohaven (搜索), suspending new enrollment in the Phase 2 RISE2 trial.
The hold stems from rodent non-clinical toxicology findings involving a specific opacalim (搜索) metabolite; the FDA wants data on whether the toxicity is rodent-specific.
SK Biopharmaceuticals (搜索) says it knew of the findings during due diligence and that no related adverse events have appeared among more than 1,200 patients dosed to date.
The U.S. Food and Drug Administration has placed a partial clinical hold on opacalim (搜索) (BHV-7000), the investigational epilepsy drug candidate that SK Biopharmaceuticals (搜索) is in-licensing from Biohaven (搜索), temporarily suspending new patient enrollment in the Phase 2 RISE2 trial while allowing patients already receiving treatment to continue therapy.
SK Biopharmaceuticals (搜索) disclosed the FDA action on Sept. 10 and held an online briefing on Sept. 11 to explain both the hold and the licensing agreement it signed with Biohaven (搜索) on Aug. 26. Yoo Chang-ho, head of strategy and business development, who led the licensing deal, attended the briefing.
Rodent Metabolite Findings Prompt FDA Request
According to the company, the FDA requested additional data to determine whether toxicity observed in preclinical studies — in which a specific metabolite of opacalim (搜索) was administered to rodents — is a rodent-specific phenomenon. The regulator asked for additional non-clinical supporting evidence to establish whether the toxicity is a species-specific effect limited to rodents.
SK Biopharmaceuticals (搜索) stressed that it had already identified the preclinical findings during several months of due diligence conducted before the contract. "We were fully aware of this issue before signing the agreement," Yoo said. "Based on our own assessment and input from outside experts, we viewed the likelihood of the same problem occurring in humans from the unusual metabolic pathway found in rats as low." He added, "We still stand by the judgment we made at the time of the contract."
The company said it analyzed the relevant data together with toxicology experts and external consultants who have prior FDA pharmacology and toxicology review experience, concluding that the toxicity is likely a rodent-specific phenomenon and that the likelihood of the same issue in humans is limited. Yoo also said the partial clinical hold "does not change our strategic decision to introduce Opacalim (搜索)."
RISE3 Unaffected as RISE2 Enrollment Pauses
More than 600 patients already enrolled and receiving the drug will continue in the trials, but new patient enrollment in RISE2 is suspended until additional preclinical data are secured. SK Biopharmaceuticals (搜索) said the Phase 3 trial RISE3 completed patient recruitment in June and is unaffected by the measure, so it will keep its plan to release top-line results in the second half of this year.
Both RISE2 and RISE3 are multicenter, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of opacalim (搜索) in patients with refractory focal-onset epilepsy (搜索). Yoo said that even with RISE2's new patient enrollment paused, the company believes recruitment can be ramped up once the hold is lifted, so there should be no change to the overall clinical timeline.
The company repeatedly argued the matter is separate from patient safety. Opacalim (搜索) has been administered to more than 1,200 patients so far, and no safety signals or adverse events related to the preclinical toxicity findings have been identified in clinical trials, it said. "To date, no related adverse events have been observed in clinical trials involving more than 1,200 participants," Yoo said.
Deal Closing Awaits Resolution
SK Biopharmaceuticals (搜索) expects the partial clinical hold to be lifted in November. "We expect Biohaven (搜索) to submit data to the FDA between late September and early October, with the issue ultimately resolved between October and November," Yoo said. "We will close the deal once this issue is resolved." Biohaven plans to submit additional non-clinical evaluation data on the specific metabolite in consultation with the FDA to expeditiously lift the hold.
SK Biopharmaceuticals (搜索) confirmed it has not yet paid Biohaven (搜索) the $400 million upfront payment, and the two sides are in talks to close the transaction after resolving the FDA issue. The Aug. 26 global licensing agreement is worth up to $795 million (about 1.1 trillion won) and covers worldwide exclusive rights to opacalim (搜索), other potassium channel (Kv7) activator compounds, and the Kv7 discovery platform. Of the total upfront payment, $350 million is to be paid upon closing of the deal, with no payments made yet.
Positioning Against Existing Epilepsy Therapies
Unlike SK Biopharmaceuticals (搜索)' existing epilepsy treatment XCOPRI (cenobamate), opacalim (搜索) employs a novel mechanism of action that activates potassium channels and is designed to reduce central nervous system side effects. Opacalim is a selective Kv7.2/7.3 potassium channel (搜索) activator that controls the excitability of neurons, and the company believes it has competitive advantages in safety and tolerability compared with existing epilepsy treatments.
Opacalim (搜索) is a core drug candidate that SK Biopharmaceuticals (搜索) intends to develop as its second directly marketed U.S. new drug after cenobamate. Starting with the RISE3 top-line results in the second half of this year, the company aims to secure additional clinical results by 2028, with the goal of launching in the U.S. as early as 2029.
The company said it remains in ongoing discussions with Biohaven (搜索) regarding the FDA's requests and response strategy. An SK Biopharmaceuticals (搜索) representative said, "We are closely reviewing the relevant matters with Biohaven," adding, "We will continue to discuss the necessary steps for pursuing the lifting of the partial clinical hold in response to the FDA's requests."