uniQure Shares Plummet Over 60% After FDA Reverses Stance on Gene Therapy
Regulator's unexpected shift on data requirements for Huntington's disease drug AMT-130 creates significant uncertainty for approval pathway.
Shares of uniQure NV (NASDAQ: QURE) collapsed by more than 60% in early November trading after the company disclosed a major regulatory setback for its lead gene therapy candidate, AMT-130, for Huntington’s disease. The U.S. Food and Drug Administration has unexpectedly reversed its position on the data required for a potential accelerated approval, throwing the submission timeline into disarray and erasing months of positive momentum for the biotechnology firm.
The sell-off was swift and severe after uniQure announced that the FDA no longer agrees its Phase I/II study data may be sufficient to support a Biologics License Application (BLA). This marks a significant departure from previous regulatory guidance that had underpinned the company's strategy and investor expectations. The news sent uniQure's stock from a closing price of over $67 down to below $27, wiping out more than a billion dollars in market capitalization and hitting a new 52-week low.
The FDA's sudden change of course was a stunning blow to uniQure, particularly as it came just weeks after the company reported what it considered highly positive three-year data from the AMT-130 trial in September. Those results had shown a statistically significant slowing of disease progression and were met with optimism from analysts, with some projecting peak sales for the therapy as high as $2.5 billion. The therapy had previously been granted Breakthrough Therapy and Regenerative Medicines Advanced Therapy (RMAT) designations by the FDA, further fueling hopes for an expedited path to market.
"The feedback we received from the FDA is a drastic change from the guidance provided to us late last year," said Matt Kapusta, CEO of uniQure, in a statement addressing the news. "We are surprised and deeply disappointed by this change in regulatory guidance and the profound impact this will have on the Huntington’s disease community."
Huntington's disease is a fatal, inherited neurodegenerative disorder with no approved treatments that can delay its onset or slow its progression. uniQure's AMT-130 is a one-time administered gene therapy designed to tackle the disease at its genetic root, representing a beacon of hope for thousands of patients and their families.
Analysts were caught off guard by the development. Stifel analysts described the FDA's pivot as "very surprising" and a "shock," noting in a report that it creates a "possible overhang for the space" of gene therapies facing complex regulatory pathways. According to reporting from BioSpace, the reversal raises questions about the viability of using external, or synthetic, control arms for pivotal trials in slowly progressing neurodegenerative diseases.
The core issue centers on the FDA's new position that uniQure's trial data, which was compared to an external control group of untreated patients, may not be adequate to serve as the primary evidence for a BLA submission. The company had planned to file for accelerated approval in the first half of 2026.
With its U.S. approval strategy now uncertain, uniQure stated it will urgently request a meeting with the FDA to find a viable path forward. The company also plans to proceed with regulatory discussions in Europe and the U.K., where it hopes for a more receptive environment. Despite the setback, uniQure has a cash runway projected to last into the second half of 2027, providing some financial stability as it navigates the challenging regulatory landscape.
Investors are now left to weigh the future of a promising therapy that has been cast into doubt not by its clinical data, but by a sudden shift in regulatory requirements. The path forward for AMT-130 is now significantly longer and more complex than previously anticipated, a reality starkly reflected in the company's battered share price.