The latest update from uniQure on its gene therapy for Huntington’s disease demonstrates that it continues to slow the progression of Huntington’s disease, but at a reduced rate compared to data from 2025.
Last year uniQure reported that its drug, AMT-130, had slowed HD progression by 75 percent over a three-year period.
Breaking its promise to allow uniQure to apply for drug approval in early 2026, the dysfunctional U.S. Food and Drug Administration (FDA) recommended that the company conduct a new, full-blown clinical trial of AMT-130. After the HD community petitioned the FDA and the agency’s ineffective commissioner resigned, uniQure was allowed to submit its application, based on data from people who had completed three years in the study. It did so on September 2.
On September 29, uniQure released new data from a group of twelve clinical trial volunteers who had completed four years in the study. (Click here for the press release.)
Those individuals showed a slowing of the disease by 44 percent – an encouraging sign but, as uniQure itself acknowledged, not considered statistically significant because that improvement could have occurred by chance.
Key measures have improved
AMT-130 now has an official generic name, ifezuntirgene inilparvovec.
"Four years after a single administration, ifezuntirgene inilparvovec continues to show meaningful slowing of disease progression, further strengthening our conviction in its benefit for people living with Huntington’s disease," Walid Abi-Saab, M.D., uniQure’s chief medical officer, stated in the release.
Dr. Abi-Saab reported that at 48 months, Total Functional Capacity (TFC), a primary measure of the drug’s effect, “demonstrated consistent slowing of functional decline.” The higher doses of the drug showed greater benefit, he noted.
The updated analysis of those on the drug through 36 months also demonstrated a “substantial effect” on TFC and cUHDRS, another key measure of HD, Dr. Abi-Saab stated. These data reinforce the data already included in the application to the FDA, he added.
Scientists’ views
HD scientists have said that even if the hoped-for 75-percent slowing of HD by ifezuntirgene inilparvovec is less, it could still have a big impact on the disease.
Commenting on ifezuntirgene inilparvovec at the Huntington’s Disease Foundation’s biennial conference in August, Sarah Tabrizi, M.D., Ph.D., one of the medical leaders of the uniQure trial, said that the actual effect of the drug could be in the range of 40-50 percent, still a “fantastic” improvement, unprecedented in HD research.
"What I find particularly notable in the expanded data is the consistently meaningful treatment effect at 36 months, and the apparent stability of the functional capacity benefit through Month 48,” Victor Sung, M.D., professor of neurology at the University of Alabama at Birmingham (UAB), director of the UAB Huntington’s Disease Clinic, stated in the uniQure release. “Total Functional Capacity tracks things that matter the most to patients and families – ability to work, perform household chores and handle daily self-care activities.”
Seeing that treatment effect “maintained at four years is meaningful for people living with this relentlessly progressive degenerative disease," Dr. Sung added.
“A 44 percent slowing of disease progression, now out to 48 months, is still unprecedented and of meaningful value to this patient population,” said uniQure CEO Matt Kapusta. “It’s something no other program in Huntington’s disease has been able to achieve.”
Hopeful, but complex results
The scientist-written website HDBuzz noted the “hopeful, but complex results” in the uniQure update, including the company’s reliance on external comparators rather than a placebo. This results from the rareity of HD and the fact that ifezuntirgene inilparvovec is injected into the brain with a surgery lasting 12-18 hours.
“With only a small number of people followed for 4 years, there is uncertainty around this estimate, so the 44% figure should be interpreted cautiously,” HDBuzz wrote.
Jeff Carroll, Ph.D., a leading HD scientist at the Allen Institute and like me an HD gene carrier, reviewed the new uniQure data for STAT. Dr. Carroll was not surprised to see the treatment effect of the drug narrow, because the drug was administered to only twelve individuals.
“The fact that we continue to see any benefit in cUHDRS functional capacity scores is hugely exciting,” Dr. Carroll said.
“I’m not surprised by the four-year results because this isn’t a cure,” commented Help4HD International advocate and HD gene carrier Lauren Holder. “This is a slowing-of-disease-progression treatment, and so I would expect there’s still decline going on, and we’re going to see that on testing, and that doesn’t mean it’s not working.”
Advocates meet with FDA at HD roundtable
Before these latest actions by uniQure, and in the wake of the crises created by the former commissioner, the FDA invited representatives of six HD organizations to a meeting at its headquarters.
The hour-long lunchtime roundtable meeting on July 30 was chaired by Acting Commissioner Kyle Diamantis, along with several staff members.
So far, no HD leader has granted me an interview about this meeting. On July 31, they posted a note on Instagram thanking Diamantis for the roundtable.
“We appreciate the opportunity to bring together people with lived experience, advocates, researchers and clinicians to engage in meaningful dialogue,” the note stated. “Collaboration like this ensures the voices of the Huntington’s disease community remain at the center of research, drug development, and regulatory decision-making.”
The organizations were Help4HD, HDReach, Huntington’s Disease Foundation, Huntington Study Group, Huntington’s Disease Society of America, and Huntington’s Disease Youth Organization.
Regarding the FDA, the uniQure data update, and the company’s pending drug application, Help4HD International’s Holder said, “I honestly can’t say one way or the other when it comes to the FDA. We need to make sure we are educating people at the FDA because I don’t want them misunderstanding the numbers [data] and causing an issue.”
Holder added that she remains “very hopeful about this treatment and still very impressed with the results.”
