uniQure N.V. (NASDAQ:QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to AMT-191, uniQure's investigational gene therapy for the treatment of Fabry disease, a rare, inherited genetic disease. In August 2024, uniQure announced the dosing of the first patient in its U.S., multi-center, open-label Phase I/IIa trial of AMT-191.

"This important designation highlights the need for new gene therapies like AMT-191 for patients with Fabry disease with the potential of delivering meaningful benefit given the suboptimal effectiveness of current chronic treatments," stated Walid Abi-Saab, M.D., chief medical officer of uniQure. "This designation supports our Phase I/IIa clinical trial and we look forward to rapidly generating clinical proof-of-concept data and providing initial data in 2025."

In patients with Fabry disease, a pathogenic variant in the galactosidase alpha (GLA) gene leads to α-galactosidase A (aGAL-A) enzyme deficiency, which in turn results in a progressive accumulation of lipids in multiple cell types, including kidney and heart cells, eventually resulting in a multi-system disorder. AMT-191 is a one-time intravenously administered investigational AAV5-based gene therapy that uses a proprietary, highly potent promoter to deliver a GLA transgene designed to target the liver to produce GLA protein.

The Phase I/IIa clinical trial of AMT-191 will be conducted in the United States. The multicenter, open-label trial consists of two cohorts with up to six adult male patients each: a low-dose cohort of 6x1013 gc/kg and a high-dose cohort of 3x1014 gc/kg delivered through a one-time intravenous infusion. Patients will continue to receive their regular enzyme replacement therapy until the criteria for withdrawal is met and will be followed for a period of 24 months. The trial will explore the safety, tolerability, and early signs of efficacy by measuring the expression of lysosomal enzyme aGLA-A. Additional details are available on (NCT06270316).

The FDA's Orphan Drug Designation provides a special status for investigational drugs being developed for rare diseases considered to affect only up to 200,000 people in the United States. Orphan drug status provides certain incentives, including tax credits, grants and waiver of certain administrative fees for clinical trials as well as seven years of market exclusivity in the United States following drug approval.