LEXINGTON, Mass. and AMSTERDAM
September 29, 2026 — uniQure N.V. announced additional data from ongoing Phase 1/2 studies of ifezuntirgene inilparvovec (AMT-130) in Huntington’s disease, reporting continued slowing of disease progression through 48 months following a single administration. Among 12 high-dose patients evaluated at Month 48, the primary composite Unified Huntington’s Disease Rating Scale (cUHDRS) endpoint showed 44% slowing of disease progression versus an updated external control, although the result was not statistically significant (p=0.144). Total Functional Capacity (TFC) showed 61% slowing, with a nominal p-value of 0.008. An updated 36-month analysis including 15 high-dose patients showed 80% slowing based on cUHDRS and 67% based on TFC versus the updated external control. uniQure said the findings support continued development of AMT-130, while noting limitations associated with missing data and survivor bias in the long-term external control.
AMT-130 Shows Sustained Effects Through 36 and 48 Months
The updated clinical analysis included 29 patients treated with AMT-130 across the first two cohorts, including 17 high-dose and 12 low-dose patients. At 36 months, the 15 high-dose patients had a mean cUHDRS change from baseline of -0.28 compared with -1.39 in the propensity score-matched external control, corresponding to 80% slowing of progression with a nominal p=0.005. TFC declined by a mean of 0.27 points in treated patients versus 0.82 points in the external control, corresponding to 67% slowing with a nominal p=0.011. At 48 months, the 12 high-dose patients showed a mean cUHDRS change of -0.90 compared with -1.61 in the updated external control, while TFC changed by -0.37 compared with -0.94. A post-hoc sensitivity analysis using a prior ENROLL-HD external control produced 53.5% slowing on cUHDRS and 68.3% slowing on TFC at Month 48. These analyses are based on external controls rather than a concurrent randomized control group at the long-term timepoints.
Dose-Dependent Responses and Long-Term Data Limitations
The 48-month comparison also showed differences between the high- and low-dose groups that uniQure said were consistent with a dose-dependent treatment effect. Mean cUHDRS change from baseline was -0.91 in high-dose patients compared with -1.94 in low-dose patients, while mean TFC change was -0.30 versus -0.70, respectively. The company also reported that mean cerebrospinal fluid neurofilament light protein was 4% above baseline at Month 48 and 6% below baseline at Month 36. Interpretation of the 48-month external-control analysis is subject to substantial missing data, with missingness reaching 53% in the updated ENROLL-HD matched controls at that timepoint. uniQure said patients who discontinued external-control follow-up were progressing faster than those who remained, potentially understating progression in the comparator and the resulting treatment effect. The 48-month cUHDRS comparison did not reach statistical significance using the updated control.
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BLA Submitted as uniQure Prepares Confirmatory Development
The new data follow FDA discussions regarding the regulatory basis for AMT-130 and the company’s plans for confirmatory development. At a June 2026 Type B meeting, FDA communicated that 36-month data from 12 high-dose patients could serve as the primary basis for uniQure’s BLA submission under the accelerated approval pathway; the BLA was submitted before the current topline results and therefore did not include them. AMT-130 has received FDA Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Fast Track designations. The investigational gene therapy uses uniQure’s miQURE gene-silencing platform to target the huntingtin gene and is delivered once through MRI-guided, convection-enhanced stereotactic neurosurgery into the striatum. The program remains investigational, and the reported analyses require confirmation through ongoing regulatory review and confirmatory clinical development. The new 36- and 48-month findings provide additional longitudinal data as uniQure advances its Huntington’s disease program.
Source :uniQure press release
