The FDA is said to be making a U-turn on uniQure’s one-time gene therapy candidate for Huntington’s disease despite the treatment being hailed as a game changer.
The FDA no longer agrees that data from a phase 1/2 study of the gene therapy, coded AMT-130, are enough to support a regulatory application for approval, uniQure said Monday following a recent pre-biologics license application (BLA) meeting with the agency.
Data released in September showed the experimental treatment slowed the progression of Huntington’s by 75% after three years compared with an external control group based on a natural history study. The data came from 12 of 17 patients who received AMT-130 at a high dose tested.
Experts called the results “game-changing,” and industry watchers touted the readout as a much-needed boost for the struggling gene therapy field. UniQure's stock price surged some 300% in the wake of the readout.
Late last year, uniQure announced that it had reached an agreement with the FDA on a BLA submission under the accelerated approval pathway based on data from the phase 1/2 study using the external control comparison.
However, according to uniQure, the FDA has now backtracked on their agreement, deeming that the phase 1/2 based on an external control group is not adequate to support a bid for approval. As a result, the timing of the BLA submission for AMT-130 is now unclear, uniQure said. The company originally planned to file for an approval in the first quarter of 2026.
UniQure is surprised by the FDA’s new feedback, which is “a drastic change from the guidance” that the agency previously provided, uniQure CEO Matt Kapusta said in a Nov. 3 statement.
“This news is unexpected, and we are truly disappointed for people living with HD, who have no disease-modifying treatment options for this devastating disease,” Kapusta said. “We strongly believe that AMT-130 has the potential to bring substantial benefit to patients, and we remain fully committed to working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the U.S.”
The company said it’s now waiting to receive final minutes of the pre-BLA meeting within 30 days and will “urgently interact with the FDA to find a path forward for the timely accelerated approval of AMT-130.”
UniQure’s stock price plummeted 66% in premarket trading Monday.
Based on uniQure’s description, AMT-130 may be another casualty of the new FDA’s stance toward cell and gene therapies under Center for Biologics Evaluation and Research Director Vinay Prasad, M.D.
The FDA in July declined to approve Capricor Therapeutics’ cell therapy to treat a serious heart condition associated with Duchenne muscular dystrophy. In making that decision, the agency cited a data package that “does not meet the statutory requirement for substantial evidence of effectiveness,” the biotech explained in a press release.
At that time, Capricor CEO Linda Marbán, Ph.D., also said the company was surprised by the FDA’s decision and that it had followed the FDA’s guidance throughout the process.
Replimune also got a surprise FDA rejection for its application for an accelerated approval of an oncolytic virus therapy in melanoma. According to the biotech, the agency cited a lack of substantial evidence of effectiveness from the phase 1/2 data the company had provided. Replimune CEO Sushil Patel, Ph.D., said the issues were not raised by the agency during previous communications.
However, it was FDA’s cancer drug leader, Richard Pazdur, M.D., who played a key role in the rejection of Replimune’s drug, not Prasad, Stat reported. Replimune has since refiled its application, which the FDA has accepted, with a decision now expected by April 10, 2026.
Huntington’s advocates may push back against the FDA’s decision on uniQure’s AMT-130. But whether that opposition can reach a significant enough level to force changes, like the Duchenne community achieved with Sarepta Therapeutics’ gene therapy Elevidys, remains to be seen.
Over the summer, Prasad’s department at the FDA demanded Sarepta stop all shipments of Elevidys after liver toxicity caused two deaths in patients who were no longer able to walk independently. After protests from Duchenne patient advocates that reportedly reached all the way to President Donald Trump, the FDA backpedaled on its restrictions to allow continued Elevidys treatment in ambulatory patients. Prasad was ousted in the wake of the incident, only to be brought back a few weeks later.
The phase 1/2 data from AMT-130 have received acclamation from Huntington’s experts. During a uniQure investor call announcing the results in September, Sarah Tabrizi, Ph.D., from University College London, a recognized leader in Huntington’s, said the “game-changing” data offered “a beacon of hope” for patients. She described AMT-130’s 75% advantage, measured by the composite Unified Huntington’s Disease Rating Scale, as a “huge effect size” that “will have massive effects for patients’ lives.”
Join us at the “Cell & Gene’s Turning Point: Lessons Learned & the Road Ahead” virtual event on Thursday, November 20. In one of the sessions, Fierce Pharma Deputy Editor Angus Liu will host industry experts from the Alliance for Regenerative Medicine, Bristol Myers Squibb, Cellares, and Epicrispr Biotechnologies to discuss how the new FDA views cell and gene therapies and expectations for the future.