uniQure N.V. (NASDAQ: QURE), a biopharmaceutical company specializing in gene therapies, unveiled updated initial safety and exploratory efficacy findings from its ongoing Phase 1/2a clinical trial evaluating the investigational gene therapy AMT-191 in Fabry disease. These preliminary outcomes represent data from 11 patients enrolled in the study and were showcased at the WORLDSymposium conference held in San Diego, California.
Background on AMT-191 and Fabry Disease
AMT-191 is a candidate gene therapy utilizing adeno-associated virus (AAV) vectors designed to address Fabry disease, a rare X-linked lysosomal storage disorder characterized by the pathological accumulation of glycosphingolipids in bodily tissues. This accumulation is caused by a deficiency in the enzyme alpha-galactosidase A (α-Gal A), which normally facilitates the breakdown of globotriaosylceramide (GB3) within cells. The gene therapy aims to restore sufficient α-Gal A activity to ameliorate disease manifestations.
Clinical Trial Details and Enzyme Activity Outcomes
The updated data cut-off for this analysis was January 8, 2026. The study has enrolled patients across three dosing cohorts receiving AMT-191 at 6 × 10¹³, 4 × 10¹³, and 2 × 10¹³ genome copies per kilogram (gc/kg). All 11 treated patients exhibited increases in α-Gal A enzymatic activity following administration, with the elevation magnitude demonstrating a dose-dependent pattern. Specifically, α-Gal A activity ranged from 0.34- to 82.2-fold above the mean normal level in the lowest dose group, 1.6- to 312.52-fold in the mid-dose group, and 27.7- to 223.7-fold in the highest dose group.
These enzymatic increases were sustained throughout the observation period, varying between a minimum follow-up of four months in the mid-dose patients and more than one year in a patient from the high-dose cohort. Notably, six of the eleven patients met predefined criteria that permitted discontinuation of enzyme replacement therapy (ERT), signaling a potential clinical impact from gene therapy-induced enzyme restoration.
Safety Profile and Adverse Events
Regarding safety, plasma lyso-GB3 levels, which serve as a biomarker for Fabry disease activity, remained stable following dosing across all cohorts irrespective of ERT status up to the cut-off date. The therapy’s safety profile was generally manageable; however, some safety concerns have emerged, particularly at the mid and high dose levels.
Two patients in the mid-dose group experienced asymptomatic Grade 3 elevations in liver enzymes. These events were classified as dose-limiting toxicities after a review by an Independent Data Monitoring Committee. Consequently, uniQure has instituted a pause on additional dosing in the mid- and high-dose groups pending further safety evaluations. Both patients responded to corticosteroid treatment and remain under medical follow-up.
In the high-dose cohort, no further serious adverse events (SAEs) beyond those previously reported have been observed. Earlier reported SAEs in two patients included two events unrelated to AMT-191 (stroke and diplopia), two related events (chest pain and increased troponin), and one event possibly related to the therapy (leptomeningeal enhancement). One high-dose patient experienced an asymptomatic Grade 3 liver enzyme elevation, which resolved after corticosteroid treatment without further complications.
Regulatory and Market Response
In related news, uniQure has announced that the U.S. Food and Drug Administration (FDA) will review the data package for AMT-130, its gene therapy candidate targeting Huntington’s disease, with a Type A meeting now scheduled. This regulatory engagement reflects the company’s advancing gene therapy pipeline beyond Fabry disease.
Following the AMT-191 data release, shares of uniQure experienced a positive market reaction, trading up 6.10% to $26.01 at the time of reporting on Friday, according to real-time market data.
Key Points
- uniQure reported updated preliminary safety and efficacy data from its Phase 1/2a trial of AMT-191 in Fabry disease involving 11 patients across three dose levels.
- Enzyme activity (α-Gal A) increased in a dose-dependent manner, with some patients discontinuing enzyme replacement therapy due to elevated enzyme levels.
- The safety profile showed manageable adverse events, though dosing in mid- and high-dose cohorts is currently paused due to dose-limiting liver enzyme elevations.
- Plasma lyso-GB3 levels, a disease biomarker, remained stable after treatment in all dose groups.
- uniQure’s shares increased by over 6% following the announcement, reflecting investor interest in the trial updates.
Risks and Uncertainties
- Occurrence of asymptomatic Grade 3 liver enzyme elevations in some patients necessitated treatment pauses, highlighting potential safety risks associated with AMT-191 dosing.
- Only preliminary data with a limited number of patients and follow-up duration have been reported; longer-term efficacy and safety remain to be fully elucidated.
- Dosing pauses in mid- and high-dose cohorts may delay trial progress and affect the assessment of optimal therapeutic dosing.
- Serious adverse events previously observed in higher dose patients require ongoing monitoring to understand their relationship to the gene therapy and clinical significance.
Disclosure
This article is based solely on the information provided by uniQure and publicly available data as of the publication date. No investment advice is offered.