FDA Lifts Clinical Hold on 4D Molecular Therapeutics' Fabry Disease Gene Therapy Trial
The FDA has lifted a clinical hold on the phase 1/2 INGLAXA (NCT04519749) clinical trial for 4D Molecular Therapeutics (4DMT)’s 4D-310, an investigational adeno-associated virus (AAV) vector-based gene therapy for Fabry disease. 4DMT plans to continue enrolling patients in INGLAXA before the end of 2024 and anticipates providing an update on the program in 2025.
The FDA originally placed the hold on INGLAXA in early 2023 after 4DMT announced it was halting enrollment due to 3 instances of treatment-related serious adverse events (AEs) of atypical hemolytic uremic syndrome (aHUS) that had resolved within 2 to 4 weeks. In one participant, the AE was classified as a grade 4 dose-limiting toxicity and required temporary hemodialysis.
Updated data from INGLAXA presented at the 2024 WORLDSymposium showed clinically meaningful improvements in 5 evaluable patients treated with the gene therapy, with no clinically significant cardiac or liver toxicities reported. No new AEs assessed as greater than grade 1 in severity and deemed related to the gene therapy had occurred since the previous interim data update.
Robert Kim, MD, the chief medical officer of 4DMT, expressed satisfaction with 4D-310's clinical activity across multiple important cardiac end points and its tolerability, with the previously reported cases of aHUS having fully resolved.
In addition to 4D-310, 4DMT is developing other gene therapy products, including 4D-150 for wet age-related macular degeneration (AMD), which has shown promising results in reducing the need for standard of care injections.