Trigriluzole

Analysts said there will be debate over whether the delay for an approval decision on Biohaven\'s rare disease candidate troriluzole is linked to the FDA layoffs and restructuring.\n Biohaven is giving investors whiplash. Forty-eight hours after saying its filing was on track, the biopharma revealed the FDA has delayed an approval decision on its rare disease candidate troriluzole and plans to hold an advisory committee to discuss the application.Connecticut-based Biohaven made the original statement after the market closed Monday. At that time, the biotech said it had completed a mid-cycle review meeting for troriluzole in the neurodegenerative disease spinocerebellar ataxia, and the FDA had “not conveyed any intention of holding an advisory committee meeting.” The FDA was still on course to make its approval decision in the third quarter.Biohaven provided another update after the market closed Wednesday. By then, the company had heard the FDA is delaying its troriluzole approval decision by three months, pushing the PDUFA date back to the fourth quarter and planning to hold an advisory committee meeting to discuss the application.The company said the delay will “provide time for a full review of Biohaven\'s recent submissions related to information requests from the FDA.” The agency is yet to schedule a date for the advisory committee meeting.  William Blair analysts sent a note to investors after talking to Biohaven management, revealing the delay “was triggered by a ‘major amendment’ status, but there was no obvious large body of data submitted for review that would have triggered this.” The analysts said there will be debate over whether the delay is linked to the FDA layoffs and restructuring, but they noted that argenx faced a similar holdup in 2023. The review will provide an early look at how flexible the FDA is willing to be under its new leadership. In 2023, the agency refused to review Biohaven’s filing for approval on the strength of a study that missed its primary endpoint. Biohaven refiled for approval after linking troriluzole to a significant slowing in disease progression in a study that compared people on the drug to patients from a historical study.Patients in the historical study were “rigorously matched” to people taking troriluzole, according to the company. But the failure of troriluzole in the earlier placebo-controlled study provides ammunition for skeptics to question the improvement over historical controls. Shares in Biohaven fell 12% in premarket trading Thursday, slumping to around $17 from a Wednesday closing price of $19.66.

Armed with a recent $600-million financial boost, Biohaven was gearing up for a potential US launch of its spinocerebellar ataxia (SCA) treatment troriluzole this year. However, the company will have to wait slightly longer after the FDA postponed the action date to the fourth quarter to review additional data and accomodate an advisory committee (adcom) meeting.Biohaven’s filing for troriluzole was accepted for priority review by the FDA in February, with an original PDUFA date in the third quarter of the year. The biotech noted it recently concluded a mid-cycle review meeting and regulatory inspections with the FDA. Although no new concerns were raised about the therapeutic, the agency said it needs a three-month extension to assess recent submissions related to information requests. While the FDA did not convey any intentions of holding an adcom at the time, it has now confirmed that it will conduct one at an unspecified date before the decision. “​​We look forward to a meeting with the advisory committee to discuss troriluzole's potential to improve the lives of individuals with SCA,” said Vlad Coric, chief executive of Biohaven. Importantly, the US regulators indicated that a Risk Evaluation and Mitigation Strategy (REMS) does not appear necessary for the treatment.Troriluzole’s path to FDA filing has been rocky, having initially missed its main goal in a late-stage trial in 2022. Biohaven, however, at the time highlighted promising post hoc findings in a genetic subset of patients, accounting for approximately 41% of the study population. More recently, the biotech withdrew its EU marketing application for troriluzole after regulators questioned its effectiveness and classification as a new active substance, citing no significant efficacy difference from the approved amyotrophic lateral sclerosis drug riluzole.Analysts at HC Wainwright earlier said that owing to a lack of FDA-approved SCA therapies, an “approval [for troriluzole] is likely but not a certainty.”The delayed decision adds to Biohaven’s woes, which has been reeling under the recent failure of its bipolar mania drug and an earlier blow to its IgG protein degrader programme. The company was acquired by Pfizer for approximately $11.6 billion in 2022, although it continues to operate as an independent entity.