uniQure acknowledged today that what it called “game changing” data in September showing significant slowing of Huntington’s disease (HD) progression in patients treated with its gene therapy candidate AMT-130 may not be enough to secure FDA approval.
In a statement uniQure said that based on a recent pre-Biologics License Application (BLA) meeting with agency officials, the company “believes that the FDA currently no longer agrees” that data from the Phase I/II studies of AMT-130 may be sufficient as primary evidence in support of a BLA submission.
The about face, uniQure continued, reversed earlier guidance from the FDA supporting the company’s collection of data from the Phase I/II studies compared with an external control—guidance that was reflected in prespecified protocols and statistical analysis plans shared with the FDA before the company carried out its analyses.
“This is a key shift from prior communications with the FDA in multiple Type B meetings over the past year,” uniQure fumed. “Consequently, the timing of the BLA submission for AMT-130 is now unclear.”
That news was bad enough to spark a 62% selloff of uniQure stock as soon as the market opened this morning, as the share price plummeted from Friday’s close of $67.69 to $25.69. The price began to rebound minutes later, reaching $29.22 by 10:36 a.m. for a 57% drop.
“Ongoing turmoil”
Joseph P. Schwartz, senior managing director, rare diseases, and a senior research analyst with Leerink Partners, said the FDA’s about face evoked parallels to the agency’s issuing a complete response letter to Repligen in July for its BLA for its lead pipeline candidate RP1 (vusolimogene oderparepvec) in combination with nivolumab [marketed by Bristol Myers Squibb as Opdivo®] for the treatment of advanced melanoma.
The FDA cited heterogeneity of patient population in the single-arm Phase II IGNYTE trial (NCT03767348) plus what it called the resulting inadequacy of data from IGNYTE and of the “contribution of components” in the study design of the Phase III IGNYTE-3 trial (NCT06264180), Repligen said in July. The FDA allowed Repligen to resubmit its BLA, and accepted that application under the accelerated approval pathway, with a target decision date under the Prescription Drug User Fee Act (PDUFA) of April 10, 2026.
“Alongside other drama recently reported at FDA,” Schwartz continued, “we hope this is representative of the ongoing turmoil at the FDA and only represents a delay as we saw with REPL.”
Schwartz cited the resignation yesterday of George Tidmarsh, MD, PhD, as director of the Center for Drug Evaluation and Research (CDER) after being placed on administrative leave for personal conduct on Friday. The leave followed investor Kevin Tang filing a complaint with the FDA, after Tidmarsh in September publicly criticized Tang-owned Aurinia Pharmaceuticals’ marketed lupus nephritis drug Lupkynis® (voclosporin) in a LinkedIn post that has since been deleted. The post called for the FDA to revisit approvals of drugs such as Lupkynis that were based on surrogate endpoints.
“Urgent” interaction planned
uniQure added that it expects to receive final minutes of its pre-BLA meeting within 30 days. From there, the company said it “plans to urgently interact with the FDA to find a path forward for the timely accelerated approval of AMT-130.” The company also said it plans to advance its discussions with regulators outside the U.S., including in the European Union and United Kingdom.
uniQure previously said it planned to submit a BLA to the FDA for AMT-130 in the first quarter of 2026, with anticipated U.S. launch later that year.
Those upbeat plans followed its announcement of positive data for AMT-130 in Huntington’s. Key among those results was the statistically significant 75% slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) in patients treated with the high dose of 6×1013 gc/subject, meeting the primary endpoint of the study.
“[A] 75% slowing of disease progression is greater than what we even anticipated, expected, and hoped for,” Sarah Tabrizi, MD, PhD, director of the University College London (UCL) Huntington’s Disease Centre, told analysts on a conference call convened by uniQure to discuss the data.
Other positive topline 36-month efficacy results for high-dose patients in the Phase I/II study, which consisted of trials in the United States (NCT04120493) and in Europe (NCT05243017), included:
- A statistically significant 60% slowing of disease progression as measured by TFC, which met a key secondary endpoint of the study.
- Slowing of disease progression ranging from 59% as measured by Total Motor Score (TMS), to 88% as measured by Symbol Digit Modalities Test (SDMT), to 113% as measured by Stroop Word Reading Test (SWRT).
September surge
The better-than-expected positive data in September caused uniQure shares to more than triple to a five-year high, surging 248% from $13.66 to $47.50 the day of the announcement. Shares then rose another 11% to $52.65 the following day and climbed an additional 3% on September 26 to finish that week at $54.31.
Today, however, uniQure pointedly noted that the FDA granted AMT-130 its Breakthrough Therapy designation in April, and its Regenerative Medicines Advanced Therapy (RMAT) designation in May 2024, based upon data from the Phase I/II studies that was compared to external controls.
“We are surprised by the FDA’s feedback at the recent pre-BLA meeting, which is a drastic change from the guidance the FDA provided in November 2024 that data from the ongoing Phase I/II studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the Accelerated Approval pathway,” uniQure CEO Matt Kapusta said in a 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.
“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.,” Kapusta promised.
