Latest data show uniQure gene therapy continues to slow Huntington’s disease, but at a reduced rate

  

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.”

A Senate probe of the FDA and a letter from advocates to Trump could aid in approval of Huntington’s disease gene therapy

  

Two key political developments could aid uniQure’s effort to seek approval of its historically efficacious Huntington’s disease gene therapy, AMT-130, from the U.S. Food and Drug Administration (FDA): a senatorial probe of the FDA and a letter to President Trump from rare-disease advocates.

 

As reported widely, uniQure is preparing for yet another meeting with the FDA to discuss the potential Phase III large-scale clinical trial required by the agency to further test the efficacy of AMT-130. Since its start in 2019, the Phase I/II trial has involved some 45 people. In September 2025, uniQure revealed that 17 of the individuals receiving the highest dose of AMT-130 had a slowing of progression of HD by 75 percent. The FDA, seen by many biotech observers to have become dysfunctional under the Trump administration, then surprisingly reneged on a promise to allow uniQure to apply for approval in 2026.

 

On March 9, Wisconsin Sen. Ron Johnson, a Republican, announced that he had launched an investigation of the FDA because it had rejected drug applications for several rare diseases.

 

Senator Ron Johnson (official congressional photo)

 

Johnson described the FDA’s request for a new AMT-130 trial, which would include a deeply invasive sham surgery for participants not getting the actual drug, as “bureaucratic idiocy.”

 

AMT-130 requires a twelve-hour surgery to inject the drug deep into the brain. The sham surgery would serve as a placebo in the clinical trial.

 

“You’re expecting people to go through sham surgeries where they get holes drilled in their heads?” Johnson said. “That’s just unbelievable.”

 

As part of his probe, Johnson is seeking denial letters from the FDA. Referring to the agency, he said that the “stories are outrageous. It just appears that they’re looking for excuses to say no.”

 

The senator added: “We’re going to find out exactly what issues the FDA listed for their ‘nos’.”

 

A sham surgery could pose ‘significant risk’

 

Johnson’s office did not respond to my request for an interview.

 

Walid Abi-Saab, M.D., uniQure’s chief medical officer, told the key publication Neurology Today that a sham controlled study “could impose significant risks and burden to patients” and that some people may consider it unethical.

 

Dr. Abi-Saab added that volunteers facing the sham surgery could not access other potentially disease-modifying therapies advancing through trials involving several years of observation.

 

Early in the AMT-130 program, uniQure used a sham surgery in several individuals but then stopped precisely because of ethical concerns.

 

Advocacy groups such as the Huntington’s Disease Youth Organization (HDYO) also have cautioned against the sham surgery.

 

In a March 6 e-mail, the organization stated that the “use of a sham neurosurgical procedure – requiring participants to undergo the risks of major surgery to the head including a lengthy time period under anesthesia without the possibility of therapeutic benefit – places an unnecessary burden on individuals already facing a progressive and fatal condition.” HDYO urged the use of “alternative trial designs … while minimizing avoidable risk to participants.”

 

Seeking to restore regulatory clarity

 

According to a report by Reuters, on April 1 the Rare Disease Advocacy, Biotechnology, and Investor Coalition sent a letter to President Trump, U.S. Health Secretary Robert F. Kennedy Jr., Medicare head Mehmet Oz, M.D., and FDA Commissioner Marty Makary, M.D.

 

The letter urged the leaders to restore regulatory clarity at the FDA as it considers a new leader for the agency’s Center for Biologics Evaluation and Research.

 

Headed by Vinay Prasad, M.D., who has resigned for the second time, the Center evaluates gene therapies such as AMT-130. Dr. Prasad’s departure follows a series of controversies involving the review of vaccines, gene therapies, and biotech drugs, including reversals of FDA promises. Biopharma executives, investors, members of Congress and others have criticized his actions.

The coalition includes nearly 100 patient disease advocacy groups, biotech executives, and investors. The letter noted that the Center had become less flexible in overseeing rare disease clinical trials.

 

The group has observed a drop in rare disease investment because of the uncertainties caused by the FDA.

 

“We believe it is of the utmost importance that the FDA chooses [for the Center] a leader who understands the unique challenges of rare disease development and respects and values the views of patients and physicians,” their letter stated.

 

A chance for the FDA ‘to reset’

 

An April 1 report by the news site BioPharmDive echoed the advocates’ critical analysis of the FDA.

 

The report observed that, after a “turbulent year” at the FDA caused by “constant leadership changes” and “erratic decision making,” the agency is as “unpredictable as it’s ever been.”

 

BioPharmDive concluded that Dr. Prasad’s departure by the end of April “could give the FDA a chance to reset.”  Commissioner Makary promised to name a replacement before he leaves.

 

‘We can’t afford delays for rare diseases’

 

On February 26, Florida Sen. Rick Scott, another Republican, chaired a hearing of the Senate Special Committee on Aging, which addressed the FDA’s difficulties.

 

At the hearing, physicians, biotech leaders and rare disease patient advocates criticized the FDA for stifling innovation.

 

The hearing discussed FDA reversals of previous agreements that it had made with drug makers. One advocate pointed out that, from 2024 to 2025, the FDA had 65 percent fewer advisory committee meetings for new drugs and biologics (a medicine derived from a living organism as opposed to a chemical), including for rare diseases.

 

At the hearing, New York Sen. Kirsten Gillibrand, a Democrat, pointed out that about one in ten Americans have a rare disease. She stated that the FDA is “not working how it should be” as laid out by Congress.

 

“This is heartbreaking for patients, and it’s why we can’t afford delays and disruptions in treatment,” Gillibrand observed. “Rare diseases can progress rapidly, cause irreversible harm and, in some cases, premature death.”