FDA complete response letter cites issues in Biohaven Vyglxia NDA

Biohaven (BHVN) announced that it has received a complete response letter from the FDA for the new drug application seeking approval of Vyglxia for the treatment of spinocerebellar ataxia. FDA cited issues that can be inherent to real-world evidence and external control studies including potential bias, design flaws, lack of pre-specification and unmeasured confounding factors. The FDA official meeting minutes from discussion of the RWE study included the statement, “a large and robust treatment effect would be needed to overcome the biases of an externally controlled trial, in order for it to be used as the primary basis for substantial evidence for effectiveness.” Biohaven believes the statistical significance and clinical meaningfulness achieved on the primary endpoint and eight consecutive secondary endpoints in 206-RWE, which included consistent results across two separate, independent, third-party run, multi-center, external controls from the largest natural history studies of SCA in the United States and Europe, clearly met criteria of “a large and robust treatment effect.” In the CRL, the FDA recommended that Biohaven meet with the Division to discuss the evidence that will be needed to support a future NDA for the treatment of SCA with troriluzole. Following receipt of the CRL, Biohaven is in the process of formally requesting a meeting as soon as possible given the large number of patients who are currently being treated in the expanded access program. Biohaven remains committed to working with the FDA to find a path forward for its NDA for Vyglxia and plans to meet with the FDA to discuss potential next steps. Given the CRL, Biohaven is initiating strategic portfolio and cost-optimization measures to prioritize three key, late-stage, clinical programs with the greatest potential for value generation: key areas of focus over the near term include: clinical-stage, lead extracellular degraders for IgA nephropathy and Graves’ disease; Opakalim, Kv7 ion channel activator, pivotal trials in adult focal epilepsy and depression; and Taldefgrobep alfa, myostatin-activin pathway inhibitor for obesity and SMA. Restructuring of business priorities underway to achieve an approximately 60% reduction in annual direct R&D spend, will result in delay of non-priority programs. New data will be presented from several of Biohaven’s priority programs at an annual healthcare conference in January 2026. Vlad Coric, chairman and CEO of Biohaven said, “We are extremely disappointed on behalf of patients by this action from the Office of Neuroscience at FDA. Beyond substantial evidence of safety and efficacy, patients with rare diseases also deserve an efficient, fair and flexible regulatory process that aligns with the urgency of their high unmet medical needs. Such an approach has been mandated by Congress to empower the FDA with maximum regulatory flexibility for rare disease. As a company, we are committed to advancing innovative treatments and remain dedicated to SCA patients despite all the challenges associated with pursuing therapies for rare diseases. Real-world evidence is an important research approach to assessing and delivering new therapies for complex rare diseases but, despite FDA policy initiatives supporting such tools, the front-line review divisions are not yet embracing FDA policy for the use of real-world evidence or the application of regulatory flexibility for rare disease.”