SK Biopharmaceuticals(326030)'s epilepsy drug candidate "Opacalim (BHV-7000)" received a partial clinical hold from the U.S. Food and Drug Administration (FDA), and the company said it expects to submit additional nonclinical data to the FDA as early as the end of this month and to have the hold resolved in Oct.–Nov.
Opacalim is a candidate for which SK Biopharmaceuticals signed a global exclusive license agreement with Biohaven worth up to $795 million (about 1.1 trillion won).
The FDA requested additional data after toxic findings related to a specific metabolite were observed in rats dosed with Opacalim. As a result, new patient enrollment was temporarily suspended in the phase 2 and 3 RISE2 and RISE3 trials.
The matter surfaced about two weeks after SK Biopharmaceuticals on the 26th signed a global exclusive license agreement with Biohaven for Opacalim, follow-on potassium channel (Kv7) activators, and a drug development platform.
According to the company, existing patients on treatment can continue in the trials. RISE3 finished enrollment in June. SK Biopharmaceuticals said it identified the toxic findings during due diligence before the contract and, after reviews by internal researchers and external experts, concluded the likelihood of the same issue occurring in humans is low. It said that although more than 1,200 people have participated in the trials so far, no related adverse events have been identified.
SK Biopharmaceuticals held an online briefing on the morning of the 11th and explained the background of the FDA's partial clinical hold and plans for next steps. The following is a Q&A with Yu Chang-ho, head of strategy (CSO) at SK Biopharmaceuticals.
1) Toxicity was found in rats—does this mean safety issues have also arisen in humans?
"This clinical hold did not occur because new toxicity or serious adverse reactions were found in patients participating in the trials. In the trials conducted so far, there were no signs that issues observed in the rat study's toxicity also appeared in humans.
Opacalim has been administered to more than 1,200 patients to date. However, adverse events related to the toxicity observed in this rat nonclinical study were not identified in the clinical trials. Therefore, it is not accurate to conclude, based on the rat study results, that safety issues in humans have been confirmed with Opacalim."
2) Then why did the FDA place a partial hold on the trials?
"When Opacalim is administered, it is metabolized into other metabolites, and among them, a specific metabolite was found only in rats. Due to this specific metabolite, certain findings were observed in nonclinical toxicity tests. The FDA requested additional data to determine whether this phenomenon is specific to rodents (rats) and what relevance it has to humans. Existing trials can proceed as is, but there is a limited measure to refrain from enrolling new patients while additional data are obtained."
3) Did SK Biopharmaceuticals know about this issue before the contract?
"We were fully aware of these findings during the detailed due diligence conducted over several months before signing."
4) If so, why proceed with a contract worth about 1 trillion won?
"We reviewed it not only with our internal researchers but also with external experts, including a former FDA reviewer. The key question was whether the toxicity observed in rats could appear the same way in humans. Based on our internal review and the opinions of external experts, we assessed that the toxicity likely reflects interspecies differences due to rat-specific metabolic characteristics, and the likelihood of the same issue in humans is low. Even after the FDA's request for additional data, our scientific and strategic assessments at the time have not changed."
5) What impact is there on the ongoing clinical trials?
"More than 600 patients are currently randomized and on treatment, and their dosing is proceeding normally. RISE3 has already completed enrollment as of June, so there is no impact from the pause in new enrollment. We are maintaining the schedule to announce the top-line results in the second half of this year as planned. In RISE2, dosing continues for patients already enrolled, but new enrollment is temporarily suspended."
6) When will the additional data requested by the FDA be submitted, and when will the partial hold be lifted?
"Biohaven is expeditiously preparing the additional nonclinical data requested by the FDA. We expect to be able to submit the data around late September to early October. Biohaven anticipated that everything would be resolved in October or November."
7) Is there a possibility that Opacalim's clinical and commercialization timeline will be delayed due to this?
"If the partial hold is resolved quickly, we assess that the overall impact on the program will be quite limited. RISE3 has already completed enrollment, so there is no change to the schedule to announce top-line results in the second half of this year. For RISE2, once the hold is lifted, we can accelerate new patient enrollment, so we expect little change to the overall clinical development timeline. Biohaven is also maintaining the overall clinical development and commercialization timeline as originally planned."
8) What impact will there be on the 1.1 trillion won license agreement?
"The contract has been signed, but because it is still before transaction closing, the $400 million upfront payment has not been made. The two companies are discussing closing the transaction after first resolving the partial clinical hold."