FDA Reversal Puts Gene Therapy Approval in Limbo for uniQure

uniQure (QURE) shares plummeted over 65% in premarket trading on November 3, 2025, after the gene therapy developer disclosed a significant regulatory setback for its experimental Huntington's disease treatment, AMT-130. The company revealed that the U.S. Food and Drug Administration (FDA) had reversed its earlier stance, stating that data from Phase I/II trials comparing AMT-130 to an external control would no longer be sufficient to support a Biologics License Application (BLA) submission, according to an ADVFN report. This marked a sharp departure from prior guidance, which had indicated that such data could form the basis for an accelerated approval pathway, as noted in an Investing.com article.

The FDA's feedback, delivered during a pre-BLA meeting, left the timeline for submitting the BLA in limbo. uniQure's CEO, Matt Kapusta, described the change as "unexpected" and "a drastic change" from earlier discussions, emphasizing the disappointment for patients with Huntington's disease, who currently lack effective treatments, as reported by Investing.com. The company now plans to engage urgently with the FDA to clarify next steps, with final meeting minutes expected within 30 days, according to an El Balad report.

The reversal has compounded challenges for uniQure, which already faces financial strain. The firm reported trailing twelve-month revenue of $14.34 million, with an operating margin of -1,140.54% and a net margin of -1,387.98%, according to a GuruFocus report. Despite these hurdles, uniQure's stock had surged more than 1,100% over the past year, driven by optimism around AMT-130's potential, per Barron's. The therapy had previously secured Breakthrough Therapy designation in April 2025 and Regenerative Medicine Advanced Therapy (RMAT) status in May 2024, as noted in an EMEgypt report, both of which had supported expectations of an expedited regulatory path.

The FDA's shift highlights the uncertainties inherent in gene therapy development. While external-control data had been accepted in previous discussions, the agency now appears to demand additional evidence, potentially necessitating further clinical trials, according to an SEC filing. This could delay AMT-130's market entry, extending timelines for a therapy targeting a disease with no approved disease-modifying options.

uniQure intends to pursue parallel discussions with regulatory agencies in the European Union and the United Kingdom while continuing to collaborate with the FDA, according to a TradingView report. The company's ability to navigate this regulatory complexity will be critical, as the outcome of these discussions could determine AMT-130's future. Investors will closely watch for updates on the final meeting minutes and any new data that might address the FDA's concerns referenced in the SEC filing.