uniQure AMT-130 shows 80% disease slowing at 36 months in HD trial
uniQure has released updated data from its ongoing Phase I/II studies of ifezuntirgene inilparvovec (AMT-130), a gene therapy candidate for Huntington's disease, showing what the company describes as a substantial and durable treatment effect up to four years after a single administration.
The release covers two separate analyses from a June 2026 data cutoff. Across 15 high-dose patients at 36 months, cUHDRS showed 80% slowing of disease progression versus a propensity score-matched external control drawn from the ENROLL-HD natural history dataset (nominal p=0.005), while Total Functional Capacity (TFC) showed 67% slowing (nominal p=0.011). The 36-month timepoint is the regulatory anchor for the Biologics Licence Application (BLA) that uniQure submitted to the US Food and Drug Administration under the accelerated approval pathway; the new data postdate that submission and were not part of it.
48-month results and a data-quality caveat
At 48 months, the picture is more complex. In 12 high-dose patients, cUHDRS showed 44% slowing but did not reach statistical significance (p=0.144), while TFC reached nominal significance at 61% slowing (p=0.008). uniQure argues the 48-month figures are likely understated because 53% of data from the updated ENROLL-HD external control was missing at that timepoint, and patients who dropped out of the control were progressing materially faster than those who remained. A post-hoc sensitivity analysis using the prior ENROLL-HD dataset returned 54% slowing on cUHDRS (nominal p=0.041) and 68% on TFC (nominal p=0.001) at 48 months, lending some support to that interpretation, though post-hoc analyses carry inherent limitations.
A dose-dependent signal was also evident. At 48 months, mean change from baseline in cUHDRS was -0.91 in high-dose patients versus -1.94 in low-dose patients, a difference of 1.03 in favour of the higher dose across TFC. Victor Sung, professor of neurology at the University of Alabama at Birmingham and director of the UAB Huntington's Disease Clinic, noted that the stability of the functional capacity benefit through month 48 was "meaningful for people living with this relentlessly progressive degenerative disease."
The therapy's safety profile remained broadly stable. Five high-dose participants (17%) experienced a treatment-related serious adverse event involving central nervous system inflammation, all of which resolved fully. One low-dose patient died by suicide approximately five years after treatment; the study investigator assessed this as unrelated to the therapy, and uniQure noted that suicide rates in Huntington's disease are substantially elevated relative to the general population.
Regulatory and competitive landscape
Ifezuntirgene inilparvovec holds FDA Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations, as well as Fast Track status. The BLA was submitted on the basis of 36-month data from 12 high-dose patients, with FDA having confirmed at a June 2026 Type B meeting that this dataset would be acceptable as the primary basis for an accelerated approval submission. The new 15-patient, 36-month analysis, while nominally strengthening the effect size estimates, was not included in that submission.
Huntington's disease remains one of the highest-unmet-need areas in neurology. Approximately 75,000 people are diagnosed across the US, EU and UK, and there are currently no approved therapies that slow or delay disease progression. Wave Life Sciences and Roche have both pursued huntingtin-lowering approaches via antisense oligonucleotides, with mixed clinical results to date. uniQure's miRNA-based gene-silencing strategy, delivered via a single direct striatal infusion, is positioned as a differentiated one-time intervention. Investor focus will now turn to the FDA's review timeline under the accelerated approval pathway and to whether the confirmatory study can generate the prospective evidence needed to support full approval.