UniQure Pauses Dosing of Fabry Gene Therapy Over Liver Safety Concerns

UniQure has halted dosing in two cohorts of its Phase I/IIa trial evaluating the AAV gene therapy AMT-191 for Fabry disease after safety concerns emerged. In the study (NCT06270316), two patients receiving the medium dose (4×10¹³ gc/kg) developed Grade 3 liver enzyme elevations that were confirmed as dose-limiting toxicities following review by an independent data monitoring committee. Both patients responded to corticosteroid treatment and remain under follow-up.

As a precaution, UniQure has paused dosing in both the medium- and high-dose (6×10¹³ gc/kg) cohorts while further investigations are conducted. No additional serious adverse events were reported in the high-dose group, although earlier treatment-related cardiac findings and a case of leptomeningeal enhancement have raised additional questions.

Despite the safety concerns, AMT-191 showed early, dose-dependent efficacy, producing sustained increases in α-galactosidase A activity and stable lyso-Gb3 levels. Several patients were also able to discontinue enzyme replacement therapy. The data were presented at the WORLDSymposium in San Diego.

09-02-2026