uniQure’s Stock Plunges 49.34% Amid FDA’s Shift on AMT-130 Approval Path, Trading Volume Surges 1,410% to Rank 127th

Market Snapshot

On November 3, 2025, , closing at a sharp loss despite a surge in trading volume. , a 1,410.33% increase from the prior day, ranking 127th in market-wide trading activity. This volatility followed the announcement of regulatory feedback from the U.S. Food and Drug Administration (FDA) regarding its investigational gene therapy, AMT-130, for Huntington’s disease. The drop erased nearly all gains from a year-long rally that had seen the stock rise over 1,100% in the past 12 months, underscoring the market’s reaction to the FDA’s revised stance on the therapy’s approval pathway.

Key Drivers

The primary catalyst for uniQure’s stock collapse was the FDA’s unexpected reversal on the adequacy of Phase I/II clinical data for AMT-130. During a pre-Biologics License Application (BLA) meeting, the agency indicated it no longer accepts the use of external control data as primary evidence to support a BLA submission. This marked a significant departure from prior guidance, where the FDA had suggested such data could justify an expedited approval under the and Regenerative Medicines Advanced Therapy (RMAT) designations granted in 2024–2025. The shift created regulatory uncertainty, with the company now facing an unclear timeline for submitting its BLA and potential delays in bringing AMT-130 to market.

The FDA’s feedback disrupted a previously optimistic trajectory for AMT-130. In September 2025, uniQure had announced Phase I/II results showing a 75% reduction in Huntington’s disease progression compared to an external control group, . The therapy’s Breakthrough Therapy designation had also fueled expectations of a first-quarter 2026 BLA filing. The agency’s sudden insistence on additional evidence or alternative trial designs not only stalled regulatory progress but also cast doubt on the therapy’s viability as a near-term solution for a disease with no existing disease-modifying treatments.

Compounding the regulatory risk, the CEO of uniQure, , expressed public disappointment, emphasizing the company’s surprise at the FDA’s reversal. This sentiment resonated with investors, who had previously backed the therapy’s potential based on prior regulatory signals. The abrupt change also triggered legal scrutiny, with the launching an investigation into potential securities fraud allegations, alleging the company may have issued misleading statements or failed to disclose material risks. While the investigation’s focus remains unproven, it added to the market’s wariness of further regulatory hurdles.

The broader gene therapy sector also reacted to the news, with analysts noting the FDA’s recent trend of rejecting therapies based on single-arm or external control trials. This pattern, highlighted in rejections of Capricor Therapeutics’ DMD treatment and Replimune’s melanoma therapy, suggests a tightening of evidentiary standards under FDA leadership. For uniQure, the implications are twofold: not only does it face delays for AMT-130, but it must also navigate a regulatory environment that now demands more robust clinical data. The company’s financials—marked by negative margins and declining revenue—further amplify the stakes, as prolonged delays could strain its liquidity and investor confidence.

In response, uniQure has pledged to engage urgently with the FDA and pursue parallel discussions with EU and UK regulators. However, the absence of a clear path forward for AMT-130 leaves its future in limbo. The company’s ability to secure alternative regulatory frameworks or additional clinical data will be critical in determining whether AMT-130 can still reach patients. For now, the stock’s freefall reflects the market’s skepticism about the FDA’s revised demands and the broader challenges facing gene therapy developers in an increasingly cautious regulatory landscape.