FDA Rejects Troriluzole, Biohaven Pivots Strategy
The FDA has turned down Biohaven’s bid to secure approval for its neurological disease treatment, prompting the company to restructure priorities and slash annual R&D spending by 60%.
A Challenging Regulatory Journey
Biohaven had originally filed for approval of troriluzole in spinocerebellar ataxia, relying on data from a phase 3 study that failed to meet its main goal. While the FDA declined to review the application in 2023, the company continued exploring a path forward, holding discussions about whether real-world evidence (RWE) could back a revised submission. In September 2024, Biohaven reported positive three-year RWE results, renewing optimism around the program.
Following a three-month postponement, the FDA has said no to a request for a green light for the application supported by real-world evidence. Biohaven said the agency’s complete response letter pointed to challenges often associated with RWE and externally controlled trials, such as possible bias, design limitations, absence of predefined parameters, and unaccounted confounding variables.
These topics came up when Biohaven met with the FDA in 2024 to review its real-world evidence study. Following the agency’s feedback, the company revised its study design, opting to use only the U.S. natural history cohort as an external control group for its primary analysis. According to official meeting minutes, the FDA advised that an externally controlled study would need to show a strong and convincing treatment effect to offset inherent biases and serve as the main evidence of efficacy. Despite the agency’s caution, Biohaven’s leadership maintains that the RWE results demonstrated a treatment effect significant enough to meet that standard.
Market Reaction and Future Outlook
However, the FDA – now under new leadership and strategic direction since the 2024 discussions – determined that Biohaven’s latest submission did not provide sufficient evidence to support approval. The agency advised the company to schedule a meeting to clarify what additional data would be required for a future resubmission, and Biohaven is preparing a formal request for that discussion.
Following the announcement, Biohaven’s share price tumbled nearly 45%, falling to $7.76 in premarket trading on Wednesday, compared with Tuesday’s close of $13.95.
Although the company continues to pursue a regulatory path for troriluzole, the FDA’s decision has led it to refocus resources on other advanced-stage programs that executives believe offer stronger prospects for long-term value creation.
Reprioritizing the R&D Portfolio
Over the coming year, Biohaven plans to focus its efforts on four lead assets: the extracellular degraders BHV-1400 for IgA nephropathy and BHV-1300 for Graves’ disease, the Kv7 ion channel activator opakalim being studied for adult focal epilepsy and depression, and the myostatin–activin pathway inhibitor taldefgrobep alfa for obesity and spinal muscular atrophy.
To preserve capital, the company may suspend or slow other research initiatives, extending its available funds beyond the near term. Biohaven reported over $408 million in cash and equivalents at the end of June. The reprioritization of its portfolio is expected to reduce annual direct R&D expenditures, excluding staffing costs, by about 60%.
