Early uniQure Fabry Trial Shows Lasting Enzyme Boost, Safety Watch

Core Insights - uniQure N.V. announced updated preliminary safety and exploratory efficacy data from its Phase 1/2a trial of AMT-191 for Fabry disease, presented at the WORLDSymposium in San Diego, California [1] Trial Data - AMT-191 is an investigational AAV gene therapy for Fabry disease, a rare X-linked lysosomal disorder characterized by excessive lipid deposition in tissues [2] - As of January 8, 2026, all 11 patients in three dose cohorts (6×10^13 gc/kg, 4×10^13 gc/kg, and 2×10^13 gc/kg) showed elevated α-galactosidase A (α-Gal A) activity, which is crucial as deficiency leads to GB3 buildup and Fabry disease [2] Efficacy Observations - Dose-dependent increases in α-Gal A activity were noted, ranging from 0.34- to 82.2-fold at the lowest dose, 1.6- to 312.52-fold at the mid dose, and 27.7- to 223.7-fold at the highest dose [3] - These increases were durable, with follow-up periods ranging from over a year in the high-dose cohort to four months in the mid-dose cohort [3] Patient Outcomes - Six out of 11 patients were withdrawn from enzyme replacement therapy (ERT) after meeting criteria including elevated α-Gal A activity [4] Safety Profile - Stable plasma lyso-Gb3 levels were maintained across all dose cohorts, regardless of ERT status, indicating a manageable safety profile for AMT-191 [5] - No Serious Adverse Events (SAEs) related to AMT-191 were observed at the 4×10^13 gc/kg and 2×10^13 gc/kg doses, although two patients at the 4×10^13 gc/kg dose experienced asymptomatic Grade 3 liver enzyme elevations [5] Dose-Limiting Toxicity - The two liver enzyme elevation cases were confirmed as dose-limiting toxicity, leading to a pause in additional dosing in the mid- and high-dose cohorts pending further evaluation [6] - Both patients responded to corticosteroid therapy and are under follow-up [6] Additional Observations - At the 6×10^13 gc/kg dose, five previously reported SAEs occurred, including two unrelated (stroke, diplopia) and two related (chest pain, increased troponin) to AMT-191, along with one possibly related SAE (leptomeningeal enhancement) [7] - One patient at this dose experienced an asymptomatic Grade 3 liver enzyme elevation that resolved with corticosteroid therapy [7] Market Reaction - Following the announcement, uniQure shares increased by 6.10% to $26.01 [8]