Biohaven acknowledges its experimental drug for spinocerebellar ataxia failed in a pivotal study, but the biotech hoped results showing benefit in a subgroup would be enough to secure approval for those patients given that this rare, inherited neuromuscular disorder has no approved therapies. The FDA disagrees.

On Thursday, Biohaven said the FDA refused to review the application for the drug, troriluzole. Refuse to file letters are not public documents. According to Biohaven, the agency said the study’s failure to meet the primary endpoint “would not permit a substantive review.” The New Haven, Connecticut-based company said it plans to request a meeting to discuss the FDA’s concerns.

Spinocerebellar ataxia (SCA) affects the cerebellum, the part of the brain that governs muscle control. The worsening of muscle control from SCA eventually leads to patients requiring wheelchairs. More than 40 types of this disease have been identified, many of them linked to a particular genetic mutation. Troriluzole doesn’t address the genetic mutation. Rather, it is intended to reduce levels of glutamate, a neurotransmitter whose dysfunction is associated with many neurological disorders, including SCA.

Biohaven’s Phase 3 test of troriluzole evaluated the drug in all types of SCA. Last year, the company reported the drug failed to meet the main goal of showing, at week 48, a significant change in score according to a scale used to assess muscle control and movement. However, the company pointed to a post hoc analysis of the data showing a treatment effect in patients with SCA type 3, or SCA3. This type is the most common form of the disease and it represented 41% of the study population. The analysis showed SCA3 patients had fewer falls compared to those given a placebo, results the company said demonstrate clinically meaningful improvement. In May, Biohaven submitted a new drug application seeking approval of troriluzole for patients with SCA3.

In a note sent to investors Thursday, William Blair analyst Tim Lugo said the FDA’s decision to decline review of troriluzole was disappointing in light of other recent favorable regulatory decisions for rare disease drugs. As examples, he pointed to the approvals of Reata Pharmaceuticals drug Skyclarys for ultra rare disease Friedreich’s ataxia and Acadia Pharmaceuticals drug Daybue for Rett syndrome. Both drugs are the first approved treatments for their respective disease indications. Lugo said troriluzole may still have a path forward, but it is unlikely the FDA will change its decision without additional clinical data. That could mean Biohaven needs to conduct another Phase 3 study enrolling only SCA3 patients.

Biohaven believes troriluzole’s mechanism of action has potential applications in other neurological diseases, but clinical trial results have been disappointing so far. In 2020, the drug failed a Phase 3 test in generalized anxiety disorder. In 2021, it failed a Phase 2/3 test in Alzheimer’s disease. A Phase 3 test in obsessive compulsive disorder is ongoing.

Biohaven stands by the data produced for troriluzole in SCA. In a prepared statement, CEO Vlad Coric said that about 200 patients have been treated with the drug for up to three years and these patients have remained stable compared to the untreated natural history cohorts who showed disease progression over a similar time period. In addition to delaying disease progression, Coric said the troriluzole data also show a reduction in falls.

“The risk-benefit profile for troriluzole warranted careful consideration by the FDA for this ultra-rare disorder,” Coric said. “SCA is clearly a severely debilitating, life-threatening disease with substantial unmet need. The approximately 6,000 patients in North America at least deserved a thorough review of the data package submitted.”

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