Several gene therapy candidates for Fabry disease made substantial progress through clinical trials in 2024, marking a potential paradigm shift in treatment approaches for this rare genetic disorder.
Multiple Gene Therapy Approaches Show Clinical Promise
UniQure's AMT-191 program reached a significant milestone in August 2024 when it began dosing patients in its U.S. clinical trial. The therapy, which delivers a functional copy of the GLA gene to liver cells, is being evaluated in adults aged 18-50 who showed suboptimal response to conventional enzyme replacement therapy. The trial, currently recruiting at sites in New York and Virginia, aims to enroll twelve patients to assess safety across two dosing levels.
Parallel developments came from 4D Molecular Therapeutics, whose candidate 4D-310 demonstrated encouraging results in improving cardiac function. This therapy specifically targets heart cells, addressing a critical aspect of Fabry disease that typically shows limited response to current treatments. Data from two clinical trials indicated improvements in heart function after one to two years of treatment, along with enhanced quality of life measures for patients.
Safety and Efficacy Data Strengthen Development Programs
Sangamo Therapeutics' ST-920 (isaralgagene civaparvovec) continued to build a compelling safety profile in the Phase 1/2 STAAR trial, which has enrolled more than 30 participants. The interim data revealed only two serious adverse events - one case each of fever and muscle pain. Beyond safety, the therapy showed promising signs of efficacy, with patients experiencing:
- Stabilized kidney function
- Reduced disease severity
- Improved quality of life metrics
The FDA has indicated that approval for ST-920 could potentially be supported by data from one additional well-designed clinical trial, supplementing the existing STAAR study results. The therapy maintains orphan drug designation in both the U.S. and European Union, facilitating an expedited development pathway.
Clinical Impact and Future Implications
These advancing gene therapy programs represent different approaches to addressing the underlying cause of Fabry disease, which results from mutations in the GLA gene. While enzyme replacement therapy remains the current standard of care, gene therapy could potentially offer a longer-lasting solution by providing functional copies of the defective gene.
The diversity of approaches - from liver-targeted delivery to cardiac-specific treatment - suggests that future therapeutic options might be tailored to individual patient needs and disease manifestations. This personalized approach could be particularly valuable given the variable presentation and progression of Fabry disease among different patients.
