Trigriluzole

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.

iStock, Andrii Yalanskyi The FDA also changed its tune and is now planning to convene an advisory committee to discuss Biohaven’s application. The FDA has pushed back by three months its decision date for Biohaven ’s investigational glutamate modulator troriluzole for the treatment of spinocerebellar ataxia, the biotech announced Wednesday evening. Biohaven, whose stock slumped more than 12% in premarket trading Thursday, now expects to receive the verdict in the fourth quarter. In a note to investors early on Thursday, analysts at William Blair called the delay “surprising,” especially given the “proximity to the completed mid-cycle review.” On Monday, Biohaven also said that it had not received communication from the FDA regarding its application for troriluzole and continued to expect the regulatory decision to come in the third quarter. In its press announcement on Wednesday, Biohaven said that the regulatory delay was to give the FDA enough time to review additional data that the company submitted in response to a request from the agency. As per William Blair based on communication with Biohaven management, the FDA’s questions “were part of the routine review process,” which the company has responded to “in a timely manner.” The company also revealed that the FDA now intends to convene an advisory committee to discuss the application for troriluzole, though that meeting has not been scheduled yet. William Blair analysts said they are “not surprised by the AdCom expectation given troriluzole would represent the first FDA-approved therapy for the treatment of SCA [spinocerebellar ataxia].” Troriluzole works by modulating the neurotransmitter glutamate, a key excitatory signal. The drug candidate increases the uptake of glutamate from the synapse, in turn lowering the concentration of the neurotransmitter in the synaptic space, according to Biohaven’s website . The overall effect of troriluzole is to prevent the overexcitation of neurons. In September 2024, Biohaven unveiled topline pivotal data for troriluzole, demonstrating that the drug slowed disease progression by 50% to 70% versus untreated comparators. The troriluzole delay comes amid delays at the FDA. Last week, for instance, the regulator failed to meet its target decision date for GSK’s Nucala, which the pharma is pushing into chronic obstructive pulmonary disease. Last month, the FDA also ran into delays for Stealth BioTherapeutics ’ Barth Syndrome application and Novavax ’s COVID-19 vaccine. William Blair addressed this possibility directly in its note. “There will be investor debate over whether this is a sign of FDA delays as a result of layoffs and restructuring at the agency,” the analysts wrote, however noting that the FDA has had a history of extending reviews in the neuroscience space. In January 2023, for example, argenx’s supplemental application for Vyvgart Hytrulo in myasthenia gravis also ran into a regulatory delay , William Blair said. Despite the delay, “we remain optimistic that the FDA will show more regulatory flexibility” toward troriluzole “given the rare-disease nature of SCA, lack of treatment options for the disease, and troriluzole’s risk/benefit,” the analysts added.