Gene Therapy Slows Huntington Disease Progression in Pivotal Trial

Topline data were announced from a pivotal phase 1/2 study evaluating AMT-130 in patients with Huntington disease (HD). 

AMT-130 is a one-time, investigational gene therapy that is administered through magnetic resonance imaging-guided, convection-enhanced stereotactic neurosurgical delivery into the striatum. The pivotal phase 1/2 study evaluated the safety and efficacy of AMT-130 in patients with Huntington disease. 

At the time of analysis, the study compared 29 participants treated with AMT-130 (high dose: n=17; low dose: n=12) with a propensity score-matched external control taken from the Enroll-HD natural history data set (n=940 for high dose; n=626 for low dose). Among the 29 patients receiving AMT-130, 12 patients from each dosing group had attained 36 months of follow up. 

Interim results showed high dose AMT-130 slowed disease progression by 75%, as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) score, when compared with the external control (primary endpoint; cUHDRS mean change: -0.38 vs -1.52; P =.003). 

Significant slowing of disease progression, based on the Total Functional Capacity scale score (TFC; secondary endpoint), was also seen in the high dose AMT-130 group vs the external cohort at 36 months (TFC mean change: -0.36 vs -0.88; P =.033).

Favorable improvements in other assessments of motor and cognitive function (eg, Symbol Digit Modalities Test, Stroop Word Reading Test, Total Motor Score) were also observed with high dose AMT-130. Notably, the high dose AMT-130 group experienced a mean reduction from baseline in cerebrospinal fluid neurofilament light chain, a biomarker of neurodegeneration, of 8.2%.

“We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington disease,” stated Walid Abi-Saab, MD, chief medical officer of uniQure. “These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.”

AMT-130 was previously granted Breakthrough Therapy designation and Regenerative Medicine Advanced Therapy designation by the Food and Drug Administration (FDA). 

According to uniQure, the Company is targeting a Biologics License Application (BLA) submission in the first quarter of 2026. 

This article originally appeared on MPR