uniQure Reports Dose-Limiting Toxicities in Phase 1/2 Trial of AAV Gene Therapy for Fabry Disease

AMSTERDAM, Feb. 6, 2026 — uniQure disclosed that two dose-limiting toxicities have been observed in its ongoing Phase 1/2 clinical trial evaluating AMT-191, an investigational AAV5-based gene therapy for the treatment of Fabry disease. The events occurred in patients receiving a mid-level dose of the therapy, according to a company release issued Feb. 6.

The two affected patients experienced asymptomatic Grade 3 elevations in liver enzymes. In line with the study protocol, uniQure has paused further dosing in both the mid- and high-dose cohorts while an internal safety assessment is ongoing. The company reported that both patients responded to corticosteroid treatment.

No serious adverse events have been reported at the two lowest dose levels. However, five serious adverse events were previously recorded among two patients treated at the highest dose. Of these events, chest pain and elevated troponin levels were considered related to AMT-191, while one additional event was deemed potentially related to the AAV gene therapy.

Despite the safety findings, the trial has shown encouraging efficacy signals. The Phase 1/2a study enrolled 11 patients across three dose levels, all of whom demonstrated increased alpha-galactosidase A enzyme activity following treatment. Six patients were able to discontinue enzyme replacement therapy, according to uniQure.

AMT-191 is designed to deliver a functional copy of the gene encoding alpha-galactosidase A, an enzyme required to break down globotriaosylceramide lipids that accumulate in patients with Fabry disease. This lipid buildup leads to progressive organ damage and symptoms including neuropathic pain, gastrointestinal issues, and hearing loss.

The trial is intended to inform dose selection for future development of AMT-191. Analysts noted that continued evaluation of the lower-dose cohorts will be critical to determining whether an optimal balance between safety and efficacy can be achieved.

Following the announcement, uniQure shares rose to an intraday high of $27.74 on Friday, up from a prior close of $24.52, before settling at $25.69 by late morning trading.

Market attention is expected to remain focused primarily on uniQure’s Huntington’s disease gene therapy program, which has demonstrated strong efficacy but has encountered regulatory challenges with the U.S. Food and Drug Administration. Minutes from a recent Type A meeting with the FDA regarding that program are anticipated in late February or early March.