uniQure N.V. (NASDAQ: QURE) announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to AMT-191, its investigational gene therapy for Fabry disease. This designation underscores the urgent need for novel treatments for this rare, inherited genetic disorder.
AMT-191 is designed as a one-time intravenous AAV5-based gene therapy. It aims to address the root cause of Fabry disease by delivering a functional copy of the galactosidase alpha (GLA) gene to the liver, enabling the production of α-galactosidase A (aGAL-A) enzyme. Fabry disease results from a deficiency in this enzyme, leading to the accumulation of lipids in cells throughout the body, causing a multisystem disorder.
Clinical Trial Details
A Phase I/IIa clinical trial (NCT06270316) is currently enrolling patients in the United States to evaluate the safety, tolerability, and early efficacy signals of AMT-191. The multi-center, open-label trial includes two cohorts of adult male patients. The first cohort will receive a low dose of 6x1013 gc/kg, while the second will receive a high dose of 3x1014 gc/kg, administered as a single intravenous infusion. Patients will continue their existing enzyme replacement therapy until pre-defined withdrawal criteria are met and will be followed for 24 months. The trial's primary focus is on assessing the expression of the lysosomal enzyme aGLA-A.
Expert Commentary
"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."
Significance of Orphan Drug Designation
The FDA's Orphan Drug Designation is granted to investigational drugs targeting rare diseases affecting fewer than 200,000 people in the U.S. This status provides several benefits, including tax credits, grant opportunities, waiver of certain administrative fees for clinical trials, and seven years of market exclusivity in the U.S. upon drug approval.
Fabry Disease: An Unmet Need
Fabry disease, an X-linked genetic disorder, affects an estimated 1 in 40,000 to 1 in 117,000 individuals. Current standard of care involves bi-weekly infusions of enzyme replacement therapy. However, this treatment has limitations, including poor cross-correction and inefficient substrate clearance in target organs like the kidney and heart.
