Four years after a single brain infusion, people with Huntington's disease who received a high dose of uniQure's experimental gene therapy AMT-130 were still losing day-to-day abilities more slowly than matched patients who never received it, the company reported September 29. But the trial's main measure, a combined score of thinking, movement, and function, no longer showed a statistically significant difference. The mixed result comes as the FDA decides whether to formally accept the company's application.
Update Note: This article reports new four-year trial results for AMT-130 (ifezuntirgene inilparvovec) following MedicalDaily's earlier coverage of uniQure's FDA filing. The newest figures come from uniQure's announcement of the four-year data, released September 29, 2026. The data run through a June 30, 2026, cutoff.
For families, the two numbers answer different questions. One asks whether the disease as a whole is slowing. The other asks whether a parent can keep working, manage money, do chores, and care for themselves. The second measure held up, and many clinicians consider it the most meaningful. The first did not, and that raises fair questions about how regulators will read the evidence.
Four-Year Results Split Between Daily Life and the Main Score
In 12 high-dose patients followed for 48 months, the composite Unified Huntington's Disease Rating Scale (cUHDRS) showed 44% slower progression than a matched external comparison group. That difference was not statistically significant, meaning chance could not be ruled out. The comparison group came from Enroll-HD, a large natural history study of people with Huntington's.
Total Functional Capacity (TFC), which scores a person's ability to work, handle finances, perform household tasks, and manage self-care, showed a 61% slower decline. The company reported that result with a nominal p-value, a label signaling it was not the pre-specified primary test. "TFC is the most direct measure we have of what patients and families care about," uniQure CEO Matt Kapusta said, according to Fierce Biotech, which reported that the company's shares fell 41% when trading began.
The company argues the four-year comparison understates the benefit. By that point, 53% of follow-up data were missing in the updated control group, and patients who dropped out were declining faster than those who stayed. When uniQure reran the numbers against the older control dataset used in its filing, cUHDRS slowing rose to 54%. That was a post hoc analysis, done after the fact rather than planned.
MedicalDaily Evidence Check: This is a small, early-stage Phase I/II study compared with registry patients, not a randomized, placebo-controlled trial. The four-year analysis includes only 12 high-dose patients, and the results have not been peer-reviewed. Separate three-year data, now covering 15 high-dose patients, showed 80% slowing on cUHDRS. These findings do not change current Huntington's care.
On safety, five high-dose participants had serious brain inflammation that fully resolved. One low-dose participant died by suicide about five years after treatment, which the study investigator judged unrelated to the therapy. People with Huntington's face a higher suicide risk than the general population. Anyone who is struggling can call or text 988.
Families Weighing Hope Against an Unsettled Approval Path
uniQure submitted its application for accelerated approval on September 2 and requested priority review, as MedicalDaily previously reported. That application rests on three-year data, not the new four-year results. Since then, the practical question for households has shifted from whether a filing would happen to how the FDA will weigh evidence that looks weaker at year four.
The company expects an FDA decision on whether to accept the application in the fourth quarter. uniQure's chief medical officer, Dr. Walid Abi-Saab, told investors it was "difficult to speculate" whether the agency would rerun the analysis with the newer control data, Fierce Biotech reported. Acceptance would start the formal review. It would not mean approval.
The families most affected are people in early-stage Huntington's who resemble trial participants, relatives at risk who are weighing genetic testing, and caregivers planning years ahead. "With only 12 high-dose participants in the four-year analysis, these findings deserve both hope and careful scrutiny," wrote HDBuzz, an independent Huntington's research news site run by scientists, in its plain-language analysis of the results. It also noted that movement symptoms and one thinking-speed test did not show slowing at four years.
Access would remain a hurdle even with approval. The therapy requires MRI-guided neurosurgery at specialized centers, which means travel, time off work, and caregiver strain. No price has been announced, and no insurance coverage policies exist.
Open Questions Families Can Bring to Their Care Team
Several key facts remain unknown. The FDA has not said whether it will accept the application, grant priority review, or ask for new analyses. It is unclear how long any benefit lasts beyond four years, and the full data have not yet appeared in a peer-reviewed journal.
For now, the reasonable step is a conversation, not a change in treatment. Patients and caregivers can ask a Huntington's specialty center about eligibility criteria, open clinical trials, and what records might be needed if the therapy is approved. The Huntington's Disease Society of America keeps a directory of Centers of Excellence and offers social work support. Nobody should stop or change current medications because of trial news.
Relatives at risk should speak with a genetic counselor before testing. Symptoms such as new depression, thoughts of self-harm, sudden falls, or trouble swallowing need prompt medical attention regardless of trial news.
Developing timeline: In June 2026, the FDA said three-year data from 12 high-dose patients could serve as the primary basis for an application under the accelerated approval pathway. On September 2, 2026, uniQure filed for accelerated FDA approval using three-year data. On September 29, 2026, the company reported the four-year results.
AMT-130's signal on daily function has held for four years in a very small group, while its main score weakened. Families should watch for the FDA's acceptance decision later this year, which will be the next clear sign of where the therapy is headed.
Key Questions Answered
What did uniQure report on September 29? Four-year data showing a 61% slower decline in daily functioning among 12 high-dose patients, while the main composite score showed a 44% slowing that was not statistically significant.
What is the difference between cUHDRS and TFC? cUHDRS combines thinking, movement, and function tests. TFC focuses on everyday abilities such as working, managing finances, household chores, and self-care.
Does this affect the FDA application? The application is based on three-year data. The FDA has not said whether it will consider the four-year results, and an acceptance decision is expected in the fourth quarter.
Is AMT-130 available now? No. It is investigational and available only in clinical trials. It has not been approved in any country.
Is the therapy safe? Five high-dose patients had serious brain inflammation that resolved. Long-term safety is still being studied.
What should families do now? Talk with a Huntington's specialty center about trials and eligibility, and do not change current medications based on this news.
Published by Medicaldaily.com
