FDA Responds to Biohaven's VYGLXIA Application for Spinocerebellar Ataxia Treatment

Biohaven Ltd. recently announced that it received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) concerning its New Drug Application (NDA) for VYGLXIA (troriluzole), intended for the treatment of spinocerebellar ataxia (SCA). This marked a significant moment for both Biohaven and the SCA patient community, which is known for lacking effective treatment options.

The clinical development of troriluzole was historic, as it laid the groundwork for the first series of industry clinical trials aimed at demonstrating therapeutic benefits in individuals affected by a particularly rare and challenging neurodegenerative disease. The data derived from the new drug application bolstered the argument for its therapeutic potential, showing that patients treated with troriluzole experienced a remarkable 50-70% slowdown in disease progression relative to those who did not receive the treatment.

Further supporting the efficacy of troriluzole, the clinical trials reported a significant decrease in adverse events linked to falls, a common and dangerous issue for those with SCA. Furthermore, the studies indicated that treatment with this drug resulted in tangible improvements in patients' ability to maintain mobility and perform daily activities. These favorable results were derived from studies including a substantial three-year real-world evidence research project (Study 206-RWE), which the FDA had previously reviewed and found to achieve statistical significance across key efficacy endpoints.

However, the FDA's issuance of the CRL arose from concerns regarding the inherent biases and potential design flaws typically associated with real-world evidence studies and external control groups. They stated that despite observing positive outcomes, significant evidence would be necessary to mitigate biases often seen in such trials. This feedback stemmed from an official FDA meeting held in March 2024, where FDA representatives articulated the necessary characteristics for substantial evidence of effectiveness.

Biohaven has expressed disappointment regarding the FDA's decision, particularly after having followed guidance for the statistical analysis plan and study protocol stipulated by the agency. Vlad Coric, M.D., Biohaven's CEO, emphasized the importance of creating efficient regulatory paths for rare diseases, particularly when it comes to fulfilling unmet medical needs. He stressed that such flexibility is crucial for patients seriously impacted by conditions like SCA, which currently has no approved treatments.

The complexity surrounding the NDA for VYGLXIA has raised questions about the FDA's ability and willingness to accommodate evolving scientific standards and real-world data evidence, thereby enhancing treatment access for patients afflicted by rare diseases. Experts, including neurologists from prestigious institutions like Harvard Medical School, have voiced their concerns about the regulatory process, arguing that it has neglected the input of clinical experts who understand the urgency faced by SCA patients.

In light of the CRL, Biohaven now faces the challenge of re-strategizing its development priorities. The company is actively working on a timely request for a meeting with the FDA to clarify the evidence needed to support a future NDA for VYGLXIA. Biohaven is committed to advancing its NDA process and acknowledges the large patient population benefitting from the expanded access program, underscoring their resolve for bringing this innovative treatment to those who need it most.

In their response to these setbacks, Biohaven is also engaging in strategic portfolio management that focuses on cost optimization, aiming for an approximately 60% reduction in annual direct research and development expenses. This redirection of resources will allow them to concentrate on three critical clinical programs known for their high value potential.

These programs include clinical-stage treatments targeting IgA nephropathy and Graves’ disease, and ongoing pivotal trials involving Opakalim, a Kv7 ion channel activator. Furthermore, they are optimistic about presenting new data from their prioritized projects at a notable healthcare conference scheduled for January 2026.

With estimates placing the number of SCA patients at around 15,000 in the United States alone, the countdown for effective treatment continues. As the landscape of rare disease treatment evolves, the need for regulatory structures that adapt to scientific insights is increasingly crucial, for both patients in dire need and the companies striving to innovate on their behalf.