UniQure Reports 44% Disease Progression Slowing in AMT-130 Huntington’s Trial at 48 Months

48-Month Trial Results and Primary Endpoint Data

UniQure filed the 48-month data through an SEC 8-K form detailing clinical findings updated to June 30, 2026. Evaluating 12 patients in the high-dose cohort, the composite Unified Huntington’s Disease Rating Scale (cUHDRS) demonstrated a 44% slowing of disease progression against the latest Enroll-HD B external control group, which included 1,337 participants. However, the result yielded a nominal p-value of 0.144, missing the threshold for statistical significance.

Under the primary endpoint measurement, the mean change from baseline for the high-dose group reached -0.90, compared with -1.61 for the control cohort. Meanwhile, the key secondary endpoint—Total Functional Capacity (TFC)—demonstrated a 61% slowing of disease progression with a nominal p-value of 0.008, showing a mean change of -0.37 for high-dose patients versus -0.94 for the control group.

Component Analysis and Functional Measures

Within the cUHDRS component evaluations, the Stroop Word Reading Test (SWRT) achieved statistical significance with a 113% slowing of decline, recording a p-value of 0.006. Other functional and motor assessments showed positive trajectories without reaching formal statistical significance. The Symbol Digit Modalities Test (SDMT) recorded a 20% slowing with a p-value of 0.731, while the Total Motor Score (TMS) demonstrated a 5.6% slowing with a p-value of 0.908.

UniQure stated that the cUHDRS trajectories between the high-dose and low-dose cohorts continued to diverge, indicating that a dose-dependent effect was maintained through the 48-month observation window.

External Control Group Comparisons and Post-Hoc Analysis

The company addressed potential confounding factors within the Enroll-HD B external control group, pointing to data missingness and survivor bias. UniQure noted that participants with longer follow-up intervals tended to exhibit slower rates of disease progression, resulting in a control population skewed toward slower-progressing patients. By the 48-month mark, data missingness in the Enroll-HD B group reached 53%, and the overall cUHDRS decline for that cohort measured -1.65, which was 20% smaller than the -2.05 decline recorded in the older Enroll-HD A natural history dataset.

To examine the impact of control group selection, UniQure provided a post-hoc analysis using the Enroll-HD A cohort of 619 participants. Against this historical control group, the 48-month cUHDRS evaluation for high-dose patients showed a 54% slowing of progression with a nominal p-value of 0.041, while TFC demonstrated a 68% slowing with a nominal p-value of less than 0.001.

36-Month Cohort Expansion and Biomarker Stability

UniQure also updated findings from the 36-month evaluation by expanding the high-dose analysis set from 12 to 15 patients. Against the Enroll-HD B control group, the expanded 15-patient cohort showed an 80% slowing in cUHDRS progression with a nominal p-value of 0.005, and a 67% slowing in TFC with a nominal p-value of 0.011. For comparison, the earlier 36-month data cut featuring 12 patients—which served as the basis for Biologics License Application (BLA) and Marketing Authorisation Application (MAA) discussions—demonstrated a 75% cUHDRS slowing and a 60% TFC slowing.

Biomarker data tracking cerebrospinal fluid neurofilament light chain (NfL) levels showed stabilization near baseline measurements from 18 months through four years. At the 48-month interval, average NfL levels in the high-dose group registered 4% above baseline, while the low-dose group recorded an 8% decrease. Company data indicates that untreated early-manifest Huntington’s disease patients typically experience annual NfL increases of 10% to 15%.

Safety Profile and Participant Tolerability

AMT-130 maintained a manageable overall safety and tolerability profile throughout the extended evaluation. Procedural adverse events remained the most frequent occurrences, and all affected participants recovered. No new treatment-related serious adverse events emerged in cohorts 1 and 2 following September 2025. One treatment-related serious adverse event involving central nervous system inflammation occurred in cohort 4, which resolved completely following a short course of corticosteroid treatment. One suicide was recorded in the low-dose group approximately five years post-treatment, which investigators assessed as unrelated to the therapeutic agent.