Learnings from Patient Mortality after Delandistrogene Moxeparvovec Administration: A Report of Two Cases and Expert Committee Considerations for Future Mitigation and Management - PubMed
8 days ago
- #gene therapy
- #Duchenne muscular dystrophy
- #acute liver failure
- Delandistrogene moxeparvovec, an AAVrh74-based gene therapy for Duchenne muscular dystrophy, is associated with acute liver injury (ALI).
- Two fatal cases of acute liver failure (ALF) occurred in nonambulatory patients (ages 15 and 16) after delandistrogene moxeparvovec administration.
- Both patients showed abrupt elevations in aminotransferases around 4 weeks post-treatment, followed by declining enzymes and rising bilirubin, indicating severe hepatocellular injury.
- An expert panel found no single biomarker or clinical feature consistently predicted rapid progression from severe ALI to ALF.
- Treatment recommendations for severe ALI include monitoring liver biomarkers and considering intravenous methylprednisolone as initial therapy.
- The panel hypothesized that delandistrogene moxeparvovec-related ALI is T-cell-mediated and discussed additional immunosuppression options.
- Enhanced baseline evaluation for hepatic comorbidities was recommended, including lipid profiling, transient elastography, and abdominal ultrasound.
- There was strong support for generating more real-world evidence and conducting prospective clinical trials to improve ALI management.