FDA Reversal on UniQure's Huntington's Gene Therapy Sends Shockwaves Through Pharma Industry

In a surprising turn of events, the U.S. Food and Drug Administration (FDA) has apparently reversed its stance on UniQure's promising gene therapy for Huntington's disease, AMT-130. This unexpected development has sent ripples through the pharmaceutical industry, raising questions about the regulatory landscape for gene therapies and the future of treatments for this devastating neurodegenerative disorder.

FDA's Abrupt Change in Position

UniQure revealed on Monday that the FDA no longer considers the data from the Phase I/II study of AMT-130 sufficient to support a Biologics License Application (BLA). This marks a significant departure from previous communications between the company and the agency. UniQure CEO Matt Kapusta expressed surprise at the FDA's feedback, calling it "a drastic change from the guidance the FDA provided in November 2024."

The company had been working closely with the FDA over the past year to ensure alignment on protocols and statistical analyses. In April, the FDA had even granted AMT-130 a special classification to expedite its review timeline. UniQure had planned to file for approval in the first quarter of 2026, but the timing is now uncertain.

Promising Clinical Data Meets Regulatory Hurdle

The FDA's reversal is particularly striking given the positive clinical data recently reported by UniQure. In September, the company announced that AMT-130 had shown a 75% slowing of disease progression in Huntington's patients after three years of treatment. This result exceeded analysts' expectations and was hailed as a potential game-changer for patients.

Sarah Tabrizi, Ph.D., from University College London, a leading expert in Huntington's disease, had described the data as offering "a beacon of hope" for patients. She noted that the 75% advantage demonstrated by AMT-130 represented a "huge effect size" that could have "massive effects for patients' lives."

Industry-Wide Implications and Regulatory Uncertainty

The FDA's about-face on AMT-130 is not an isolated incident. Recent months have seen similar surprises for other pharmaceutical companies, including Replimune and Capricor Therapeutics, whose approval applications were rejected despite previous alignment with the FDA.

Analysts suggest that these developments reflect a broader shift in the FDA's approach to cell and gene therapies under the leadership of Vinay Prasad, M.D., director of the Center for Biologics Evaluation and Research. Paul Matteis, an analyst at Stifel, commented that the situation highlights unprecedented uncertainty in predicting FDA decisions, stating, "Really the broader takeaway here for us is that FDA — and our ability to predict the FDA — is about as uncertain as it's been in the past decade or longer."

The news has had immediate financial repercussions, with UniQure's stock price plummeting by more than 65% following the announcement. The broader gene therapy sector may also feel the impact, as investors reassess the regulatory risks associated with these innovative treatments.