FDA accepts Biohaven's resubmission of rejected ataxia drug Vyglxia and plans a panel

Biohaven disclosed in a regulatory filing on Thursday that the FDA has accepted its resubmitted application for Vyglxia (troriluzole) in spinocerebellar ataxia, a group of rare inherited neurodegenerative disorders. The agency plans to hold an advisory committee and expects to issue a new decision in the first quarter of next year, according to Biohaven ¹.

What the FDA objected to

The FDA issued a complete response letter for the application on 4 November 2025 ². The filing rested chiefly on Study 206-RWE, a three-year real-world evidence study that compared patients treated with troriluzole against matched untreated external controls drawn from natural history studies in the United States and Europe. Biohaven reported that disease progression slowed by 50-70% in that comparison ². The company also cited a more than 50% reduction in the risk of falls against placebo in the safety analysis of Study 206, a one-year double-blind, placebo-controlled trial ².

The agency was not persuaded. Its letter pointed to issues that can come with real-world evidence and external control designs, naming potential bias, design flaws, lack of pre-specification and unmeasured confounding ². FDA meeting minutes from 8 March 2024 had already told the company that only a very large treatment effect would offset the biases of an externally controlled trial if it were to serve as the primary evidence of effectiveness ². An advisory committee was planned during that first review and then cancelled weeks before it was due to meet ².

Biohaven has now refiled with what its filing calls “new positive supportive analyses” ¹. The sources do not describe what those analyses contain. Europe has been no easier: Biohaven withdrew its marketing application there after evaluators questioned the supportive evidence ¹.

What it means for the market

The case is a live test of how far the FDA will accept externally controlled real-world data as the main basis for approval in a rare disease. Sponsors building rare disease programmes around natural history comparators, and the data vendors that supply them, have a direct interest in the outcome. The FDA has recently reversed several decisions made by its former leadership and has signalled a wish to be more flexible with rare disease medicines ¹.

Investors read the news as a better chance of approval. Biohaven shares rose by about 25% on the disclosure ¹. TD Cowen analyst Tyler Van Buren wrote that scheduling the panel “substantially increases the probability of approval” ¹. If cleared, Vyglxia could be the first marketed medicine for spinocerebellar ataxia, and some analysts have forecast annual sales above $1 billion ¹.

The commercial stakes for Biohaven are high. After the rejection the company moved to cut annual direct R&D spend by about 60% and narrowed its focus to three late-stage programmes: extracellular degraders in IgA nephropathy and Graves' disease, the Kv7 activator opakalim in focal epilepsy and depression, and taldefgrobep alfa in obesity and SMA ².

Caveats

The evidence base has not changed in kind. The efficacy claim still depends on an external control comparison, the design the FDA criticised, and the content of the new analyses has not been made public in the sources ¹². RBC Capital Markets analyst Leonid Timashev said the shift in FDA stance “opens a real possibility” of approval, but cautioned that the outcome could hinge “largely on how extensive those flexibility changes have been.” ¹ The date of the advisory committee has not been given; the decision is expected in the first quarter of next year ¹.