Biohaven Therapeutics, Ltd. – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Biohaven Therapeutics, Ltd. regarding its New Drug Application (NDA 210862) for troriluzole capsules, intended for spinocerebellar ataxia. The agency determined that substantial evidence of effectiveness had not been established. The primary concern revolved around Study 206-RWE, an externally controlled study, which the FDA deemed not an "adequate and well-controlled investigation" as defined under CFR 314.126. This was due to significant design flaws and methodological limitations introducing bias. Key issues included limited comparability between trial subjects and external controls, insufficient matching for critical confounding factors, and potential selection and expectation biases from site overlap. Furthermore, the study suffered from substantial missing data, systematic timing discrepancies in assessments, and fundamental differences in measurement methodologies. The FDA previously communicated concerns that this post hoc, externally controlled study, which was neither blinded nor prespecified, would be insufficient for demonstrating effectiveness. Biohaven must address these deficiencies to pursue approval.