Biohaven is proposing troriluzole for the treatment of spinocerebellar ataxia, a group of rare, genetic diseases that lead to the progressive loss of control over movement.
After a three-month delay, the FDA declined to approve Biohaven’s glutamate modulator troriluzole for the treatment of spinocerebellar ataxia. On the heels of that rejection, Biohaven has initiated a sweeping cost-optimization initiative to maximize its resources.
In its complete response letter, the FDA pointed to problems with Biohaven’s data package, though the biotech insisted in its announcement that the FDA’s concerns “can be inherent” to real-world evidence studies, which formed the foundation of its application for troriluzole. Among the issues raised by the regulator are “potential bias, design flaws, lack of pre-specification and unmeasured confounding factors,” according to Biohaven.
Shares of Biohaven are trading at $7.60 before the opening bell on Wednesday, 44.8% lower than its previous closing price of $13.95.
To manage the impact of troriluzole’s rejection, Biohaven is focusing its resources on a handful of its late-stage programs: BHV-1400 for IgA nephropathy, BHV-1300 for Graves’ disease, the Kv7 ion channel activator opakalim for epilepsy and depression and the myostatin-actin pathway blocker taldefgrobep alfa for obesity and spinal muscular atrophy. The company expects to present new data for some of these programs early next year.
Biohaven is also cutting back its annual R&D spending by 60%, though the biotech hasn’t yet said if these measures will result in layoffs.
Writing to investors on Wednesday morning, analysts at William Blair called the rejection “disappointing” and said it raises “potential liquidity ramifications.” In April, Biohaven entered into a financing agreement with Oberland Capital Management, which promised to give the biotech up to $600 million in capital, contingent on certain milestones. A $150-million tranche of this funding was dependent on troriluzole’s approval.
More broadly, William Blair noted that the Tuesday rejection could portend larger shifts in the FDA’s thinking on the use of natural history studies, particularly in rare neurological disorders, similar to Biohaven’s case. Earlier this week, uniQure ran into a similar regulatory roadblock: despite previously aligning with the FDA on the design of a Phase I/II Huntington’s disease trial for its gene therapy, the agency appears to have changed its tune and now no longer agrees that evidence from this study will be sufficient to back a biologics license application.
“The question will now be if the FDA is becoming more restrictive despite sponsors aligning on prior feedback,” William Blair wrote.
Biohaven pointed to such prior regulatory alignment in its news release on Tuesday. Citing the official minutes of its March 8 meeting with the FDA, the biotech disclosed that the agency said “a large and robust treatment effect would be needed” to outweigh the biases associated with a real-world, externally-controlled study.
Data released in September 2024 demonstrated that troriluzole slowed patients’ decline by 50% to 70% versus untreated external comparators. The drug also delayed disease progression by 1.5 years to 2.2 years. “Biohaven believes the statistical significance and clinical meaningfulness” of these findings meet the bar for such a treatment effect, the company said on Tuesday.
