uniQure Reports Positive Data on Gene Therapy for Huntington’s Disease

uniQure, a leading gene therapy company, announced additional data from ongoing Phase I/II studies of ifezuntirgene inilparvovec (AMT-130) for the treatment of Huntington’s disease. The data, which includes results from 12 high-dose patients at 48 months, continue to show meaningful slowing of disease progression, further supporting the potential of the gene therapy.

At 48 months, the primary endpoint of the composite Unified Huntington’s Disease Rating Scale (cUHDRS) showed a 44% slowing of disease progression, although this did not reach statistical significance (non-significant p=0.144). The Total Functional Capacity (TFC) also demonstrated a 61% slowing of disease progression (nominal p=0.008).

The updated data reflecting all 15 high-dose patients at 36 months showed a substantial treatment effect on both cUHDRS and TFC. The new analysis demonstrated an 80% slowing of disease progression based on cUHDRS (nominal p=0.005) and 67% based on TFC (nominal p=0.011).

A post-hoc analysis using the prior ENROLL-HD external control showed that the 48-month analysis indicated a 54% slowing of disease based on cUHDRS (nominal p=0.041) and 68% based on TFC (nominal p=0.001).

Topline clinical data at 36 months and 48 months were compared to propensity score-matched external controls from an updated ENROLL-HD natural history dataset with a June 30, 2026, data cutoff. The Company’s analysis of the updated control showed that patients discontinuing follow-up were progressing faster than those remaining in the control group, likely understating disease progression in the control and the resulting treatment effect of ifezuntirgene inilparvovec at 48 months.

At 36 months, the high-dose results showed a 80% slowing of disease progression based on cUHDRS (nominal p=0.005) and 67% based on TFC (nominal p=0.011). The treated patients had a mean change in cUHDRS from baseline of -0.28 compared to a change of -1.39 for the external control, a favorable treatment difference of 1.12 compared to baseline. For TFC, the treated patients had a mean change from baseline of -0.27 compared to a change of -0.82 for the external control, a favorable treatment difference of 0.55 compared to baseline.

At 48 months, the high-dose results showed a 44% slowing of disease progression based on cUHDRS (non-significant p=0.144) and 61% based on TFC (nominal p=0.008). The treated patients had a mean change in cUHDRS from baseline of -0.90 compared to a change of -1.61 for the external control, a favorable treatment difference of 0.71 compared to baseline. For TFC, the treated patients had a mean change from baseline of -0.37 compared to a change of -0.94 for the external control, a favorable treatment difference of 0.57 compared to baseline.

In a post-hoc sensitivity analysis using the prior ENROLL-HD external control, the 48-month analysis showed a 53.5% slowing based on cUHDRS (nominal p=0.041) and 68.3% based on TFC (nominal p=0.001).

The dose comparison at 48 months showed that the observed differences between the high and low doses were consistent with a dose-dependent treatment effect. At 48 months, the mean change from baseline in cUHDRS was -0.91 in high-dose patients compared with -1.94 in low-dose patients, a difference of 1.03 in favor of the high dose. The mean change from baseline in TFC was -0.30 in high-dose patients compared with -0.70 in low-dose patients, a difference of 0.40 in favor of the high dose.

Ifezuntirgene inilparvovec continues to be generally well-tolerated, with a manageable safety profile at both doses. The most common adverse events in the treatment groups were related to the administration procedure, and all have resolved. As previously disclosed, five high-dose participants (17%) experienced a treatment-related serious adverse event (SAE) related to central nervous system inflammation, all of which fully resolved.

Since the September 2025 data readout, one suicide in a low-dose patient occurred, approximately five years after receiving treatment. This was assessed as unrelated to treatment by the study investigator. Suicidal ideation and completed suicide occur at substantially elevated rates in Huntington’s disease relative to the general population, and suicide is among the leading causes of death in those with the disease.

These positive data are meaningful for Huntington’s disease patients who currently have no approved disease-modifying treatment options. The results will be presented at a future scientific meeting.