Fabry Disease

Patient enrollment in the clinical trial of AMT-191, uniQure’s gene therapy candidate for the treatment of Fabry disease, is expected to begin in the first half of 2024.

AMT-191 is an investigational AAV5 gene therapy that delivers a GLA transgene designed to target the liver to produce GLA protein. In patients with Fabry disease, a pathogenic variant in the GLA gene leads to GLA enzyme deficiency which results in a progressive accumulation of lipids in multiple cell types creating a multi-system disorder. AMT-191 represents a novel potential one-time administered approach to treating Fabry disease.

Pre-clinical studies have shown that AMT-191, driven by a proprietary liver-specific promoter, results in a high degree of (lyso)Gb3 lowering, cross-correction and phenotypical correction in mice. Subsequent NHP distribution and toxicology studies have confirmed the favorable safety profile and GLA expression of AMT-191.

Fabry disease is an X‑linked genetic disorder resulting from a deficiency of GLA. The prevalence is estimated to be between 1 in 40,000 and 1 in 117,000 individuals. The current standard of care for Fabry disease is bi-weekly infusions of enzyme replacement therapy, a treatment with limited effectiveness in many patients due to poor cross-correction, with inefficient clearance of substrates in the target organs, in particular the kidney and the heart.

In November 2023, we announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for AMT-191. AMT-191 has the potential to be a differentiated gene therapy for the one-time treatment of Fabry disease, incorporating a proprietary promoter and leveraging our validated AAV5 technology comprised within HEMGENIX^®, an approved liver-directed gene therapy for the treatment of hemophilia B developed by uniQure.

In September 2024, the FDA granted Orphan Drug Designation to AMT-191. In August 2024, we announced the dosing of the first patient in our U.S., multi-center, open-label Phase I/IIa clinical trial of AMT-191.