Four weeks after uniQure asked US and UK regulators to approve its one-time gene therapy for Huntington’s disease, as Biohack reported on 2 September, the company has released its first four-year results. On 29 September 2026, uniQure shared data showing that people given a high dose of the therapy were still losing daily function more slowly than matched untreated patients, though the size of the gap shrank compared with earlier numbers1. Investors reacted sharply: the company’s stock fell 40% when the market opened that day2.
The therapy, called AMT-130 and now also known by the generic name ifezuntirgene inilparvovec, is designed to reduce production of the huntingtin protein, which drives the disease. It is given once, during brain surgery3.
What the new numbers say
The latest analyses cover 17 patients who received the high dose. Fifteen of them were included in an updated three-year analysis and 12 in the four-year analysis3.
The main yardstick at four years was Total Functional Capacity, or TFC, a score of how well people manage daily life on their own. One neurologist described it as tracking the ability to work, do household chores and handle self-care3. Over four years, TFC scores in high-dose patients fell by an average of 0.37 points, compared with 0.94 points in matched untreated patients. That works out to a 61% slower decline3.
A broader score, the composite Unified Huntington’s Disease Rating Scale (cUHDRS), which combines thinking, movement and daily living, showed 44% slower decline at four years. That difference did not reach statistical significance, meaning it could plausibly be due to chance32.
The updated three-year analysis, which now includes three more high-dose patients, looked stronger: 80% slower decline on cUHDRS and 67% slower on TFC compared with matched controls3. For comparison, the company’s original three-year readout in September 2025 reported 75% and 60% slowing on the same two scores4.
When both doses were compared at four years, with 12 patients in each group, the high-dose group showed slower progression3.
What the data do not show yet
The biggest limit is the comparison group. The treated patients are not measured against a placebo group in the same trial. They are compared with untreated people drawn from Enroll-HD, a separate “natural history” database that follows how the disease progresses on its own5. These matched outsiders were picked using a statistical method meant to make them look as similar as possible to the treated patients4.
That database brings its own problems. BioPharma Dive noted that it gets updated, which can shift results, and that more information goes missing the longer people are followed, because patients with a worsening brain disease often struggle to stay in an observational study2. At four years, data were missing for 53% of matched controls3. uniQure said this means the treatment effect was “likely understated,” and an after-the-fact analysis by the company found 54% and 68% slowing on the two scores2.
Victor Sung, a neurology professor at the University of Alabama at Birmingham, pointed to the same issue from the other direction:
“We see this even as the rate of decline in the updated comparator dataset slowed, an anticipated shift which appears to reflect some attrition in the longitudinal external control data, and which does not reflect the typical clinical presentation of accelerating decline over time,” Sung said.
In other words, the untreated group appeared to decline more slowly over time than Huntington’s usually does, which would make any treatment look less effective3. HDBuzz, a site that explains research to the Huntington’s community, called the new analyses “nuanced” and said there is “a lot of nuance in the analysis of participants against groups of controls, which could influence next steps”1.
The group sizes are also small, a dozen people at four years, and the results have been shared by the company in a press release and presentation rather than in a peer-reviewed paper1.
How the studies are set up
The data come from two early-to-mid-stage trials, one in the US and one in Europe, testing two doses in adults with early Huntington’s disease3. In the US study, 26 patients were randomly assigned to a low dose, a high dose or an imitation “sham” surgery, with a blinded first year followed by open long-term follow-up of treated patients5. The European study enrolled 13 patients in its first groups5; a later group across both regions also received drugs to calm the immune system6. The US trial registry lists an estimated 43 participants and a main completion date in June 20297.
HDBuzz reports that more than 50 people have now received the gene therapy, and 24 have lived four or more years since treatment1. On safety, the company said in 2025 that the therapy had been generally well tolerated, with the most common side effects linked to the surgery and all resolved4.
Who is behind it, and the money
uniQure, a Netherlands-based gene therapy company, sponsors both trials and released the new results27. Its chief medical officer, Walid Abi-Saab, said the therapy “continues to show meaningful slowing of disease progression” four years after a single dose3.
Outside reaction was mixed. The company lost about a billion dollars in market value on the day of the release2. Analysts at the investment bank Leerink Partners said they agreed with “all the caveats” but wrote that “AMT-130 is clearly doing something.” Stifel analyst Paul Matteis called the four-year results “still impressive generally,” while noting “some regression”2. Analysts work for firms that advise investors, not regulators.
Where approval stands
uniQure has asked the US Food and Drug Administration for accelerated approval, a route that can let a therapy reach patients sooner based on evidence “reasonably likely” to predict benefit, while requiring more testing to confirm it3. It has also applied to the UK’s Medicines and Healthcare products Regulatory Agency5. The company requested a fast review that could lead to an FDA decision in about eight months2.
The road there was bumpy. In March 2026 the FDA appeared to change its position on the trial’s design and measures; in June, the company said the agency had agreed the three-year data could serve as the main basis for an application1. The new four-year analyses were finished after the US filing, so they were not included in it3. The therapy already holds three FDA designations meant to speed development: Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Fast Track5.
What to watch next
- The FDA’s decision, expected roughly eight months after the late-summer filing under the requested fast review2.
- A confirmatory trial. Plans are underway, and TFC, the daily-function score, will be its main measure3. The company still has to agree on the design with the FDA1.
- Longer follow-up of treated patients, which the US trial plans to continue for five years5.
Huntington’s disease affects about 75,000 people in the US, Europe and the UK, and no approved treatment slows its progression, according to the company5. Whether this therapy changes that will depend on how regulators weigh small, company-reported gains against an imperfect outside comparison.
