UniQure crashes as Huntington’s gene therapy shows less slowing of disease at 4 years

News Drug Development UniQure crashes as Huntington’s gene therapy shows less slowing of disease at 4 years September 29, 2026 | 4 min read | Heather McKenzie Twitter LinkedIn Facebook Email Print The results are nevertheless “unprecedented,” UniQure executives said on an investor call Tuesday, emphasizing that the updated natural history database used as the control group for the Phase 1/2 study of AMT-130 underestimates disease progression. UniQure’s stock price plunged nearly 40% Tuesday morning as highly anticipated four-year data from its Huntington’s disease gene therapy showed a less impressive disease slowing as compared with results from a year ago.In the Phase 1/2 trial, 12 patients who received the highest dose of AMT-130—also called ifezuntirgene inilparvovec—saw a 44% slowing of disease progression after 48 months, a non-significant difference from natural history controls, uniQure said in its Tuesday announcement. This is notably less than the 75% three-year slowing of disease reported by uniQure in September 2025.The biotech’s stock fell by as much as 38% to $24.11 per share an hour after the market opened Tuesday.

Still, uniQure executives were positive on the gene therapy as they await word from the FDA on the biologics license application (BLA) it submitted earlier this month. While this missed the four-year analysis’ primary endpoint of slowing disease progression on the composite Unified Huntington’s Disease Rating Scale (cUHDRS), total functional capacity (TFC) for treated patients was 61% at four years, which was significantly better than controls. UniQure Chief Medical Officer Walid Abi-Saab noted in the release that TFC is the primary outcome in the company’s planned confirmatory study of the gene therapy, and executives emphasized on an investor call Tuesday that this metric is most reflective of quality of life for people with Huntington’s.Stifel analysts wrote in a Tuesday morning note that the four-year data “continues to clearly support a drug effect, though there is regression in efficacy on cUHDRS .

. . whereas TFC data (61% slowing) hold up.”UniQure further noted that the treatment effect generated by AMT-130 at four years is “likely understated by substantial missing data and survivor bias in [the] updated external control”—something that Abi-Saab said led to an “underestimation of disease progression” in the ENROLL-HD natural history dataset.

Post-hoc analysis using prior external control data showed a disease slowing of 54% on cUHDRS and 68% on the TFC in the same time period, the company said.Stifel elaborated on this nuance, writing that “the new results leverage an updated ENROLL-HD natural history database, which includes more patients, but also a higher rate of missing data.”As for safety, AMT-130 “continues to be generally well-tolerated, with a manageable safety profile at both doses,” uniQure said. Five patients, or 17% of those who received high-dose AMT-130, had a treatment-related serious adverse event related to central nervous system inflammation, and all of these reactions have resolved, according to the release. There was one suicide, executives noted on an investor call Tuesday morning, but this was deemed unrelated to the gene therapy.

“As pioneers in this space, we are blazing a new trail in HD, learning and deepening our understanding with every data point we generate,” UniQure CEO Matt Kapusta said on the call.Meanwhile, uniQure also shared updated three-year data from all 15 high-dose patients demonstrating a “substantial treatment effect” on both cUHDRS and TFC—the timepoint uniQure said is the “regulatory anchor” for its submitted biologics license application (BLA) and the confirmatory study. This analysis, which includes three additional high-dose patients that weren’t reported last year, showed an 80% slowing of disease progression on the cUHDRS and 67% on the TFC.Stifel emphasized the importance of these results over the four-year data. “The 3-year data here are arguably most important, since this data cut is the crux of QURE’s alignment with FDA,” the analysts wrote on Thursday.

A long, messy road UniQure announced on Sept. 2 that it had submitted regulatory applications to both the FDA and UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The biotech has requested priority review from the FDA.The BLA was a long time coming.

UniQure was set to seek approval of AMT-130 in the first quarter of this year—before the FDA last November that it “no longer agrees” that data from the Phase 1/2 trial are “adequate to provide the primary evidence in support of a BLA submission,” according to a company update at the time. Both former commissioner Marty Makary and Center for Biologics and Evaluation (CBER) director Vinay Prasad have made negative comments appearing to allude to the gene therapy. Regulatory Makary Defends FDA’s Decision-Making Amid Contentious Rare Disease Rejections Without naming a specific product, Commissioner Marty Makary referred to an investigational therapy, delivered surgically into the brain, that the FDA was “pressured” to approve even after finding no clinical benefit to patients.

February 27, 2026 · 2 min read · Tristan Manalac Read more Then, in June—with both leaders gone—the FDA again reversed course on AMT-130, agreeing that the three-year data were indeed sufficient to support an application for accelerated approval.In response to a question regarding how newly minted CBER director Karim Mikhail will respond to the application, Kapusta focused on the results.“We strongly believe in our data, and we strongly believe that what we’ve demonstrated in four years, quite frankly, is unprecedented, and that this data demonstrates that we can significantly slow disease progression, and it really doesn’t matter who’s leading CBER, who’s the commissioner of the FDA, who’s on the review team,” he said.UniQure is expecting acceptance of the BLA in the fourth quarter. Twitter LinkedIn Facebook Email Print Huntington’s disease Phase 2 Regulatory uniQure Heather McKenzie Heather McKenzie is senior editor at BioSpace and curator of the ClinicaSpace newsletter. She is an award-winning journalist specializing in rare disease and neuroscience, in addition to her extensive coverage of the FDA and regulatory science.

You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.