uniQure NV (NASDAQ:QURE) shares climbed 3.1% in premarket trading Friday after the company published preliminary findings from its Phase I/IIa study of AMT-191, an investigational one-time gene therapy for Fabry disease.
The data, encompassing 11 patients spread across three ascending dose groups, showed increased activity of the deficient enzyme α-galactosidase A (α-Gal A) in every treated individual. The company reported a clear dose response: the highest-dose cohort recorded α-Gal A activity ranging from 27.7- to 223.7-fold above normal levels. One patient in that cohort sustained supraphysiological enzyme expression for more than a year following dosing.
According to the company, six of the 11 participants satisfied predefined criteria allowing them to discontinue standard enzyme replacement therapy (ERT). Across all cohorts and irrespective of whether patients remained on ERT, plasma lyso-Gb3 concentrations were reported as stable after dosing.
Walid Abi-Saab, M.D., uniQure’s chief medical officer, said, "These updated preliminary data reinforce our confidence in the biological activity of AMT-191, including sustained and dose-dependent increases in α-Gal A activity across all dose cohorts of the treated patients."
On safety, uniQure described AMT-191 as having a manageable profile overall but disclosed two notable events: at the mid-dose level, two patients experienced asymptomatic Grade 3 elevations in liver enzymes. Those events were confirmed as dose-limiting toxicities. As a result, the company has paused additional dosing in the mid- and high-dose cohorts while it evaluates those findings further.
Fabry disease is a rare genetic condition caused by insufficient α-Gal A activity, which leads to accumulation of a certain lipid within cells. Current standard of care typically requires repeated ERT infusions; a successful one-time gene therapy could change the treatment paradigm for affected patients.
Key points
- All 11 patients in the Phase I/IIa AMT-191 trial showed elevated α-Gal A activity, with clear dose-dependent increases.
- Six patients met pre-specified criteria to stop enzyme replacement therapy, and plasma lyso-Gb3 levels remained stable post-dose across cohorts.
- Two asymptomatic Grade 3 liver enzyme elevations at the mid-dose level were classified as dose-limiting, prompting a pause in further mid- and high-dose enrollments.
Risks and uncertainties
- Safety signal: confirmed Grade 3 liver enzyme elevations in two mid-dose patients have paused additional dosing in mid- and high-dose cohorts - this directly affects clinical development timelines and risk assessments.
- Limited sample size: the data are preliminary and derived from 11 patients across three dose cohorts, which constrains the ability to generalize durability and safety across broader populations.
- Regulatory and clinical follow-up: further evaluation of the dose-limiting toxicities is required before resuming higher-dose administration, creating uncertainty around next steps in the trial.
Market and sector impact
The results are relevant to the biotechnology and rare-disease therapeutics sectors. Positive early biological activity and ERT discontinuations may influence investor sentiment toward companies developing one-time genetic treatments, while safety events can weigh on near-term clinical and regulatory prospects.