Delandistrogene moxeparvovec

Timely identification and discontinuation of culprit-drug is the cornerstone in managing drug-induced liver injury (DILI), and this study aims to thoroughly investigate the potential hepatotoxic drugs by using the FDA Adverse Event Reporting System (FAERS) database.

DILI-related reports in the FAERS database between 2004 and 2024 were used to compile a reported culprit-drug list, and the single drug and drug class with the highest reporting frequency were counted accordingly. The disproportionality analysis was used to assess the DILI risk of each reported culprit-drug.

236,918 DILI-related reports were submitted to the FAERS database between 2004 and 2024, in which 1459 drugs were reported as culprit-drug. Paracetamol is the most frequently reported single drug, while antineoplastic agents are the most frequently reported drug class. 806 of 1459 drugs showed positive signals in disproportionality analysis, among which vorasidenib is the drug with the highest signal strength, followed by floxuridine, pyrazinamide, delandistrogene moxeparvovec, and isoniazid. In the distribution analysis of positive signal drugs, antineoplastic agents have the largest number of positive drugs and occupy a dominant position among high-risk level drugs.

Our study summarized a reported culprit-drug list of DILI by comprehensively reviewing the liver injury-related reports in the FAERS database, and highlighted the prominent position of antineoplastic agents in reporting frequency, risk signal strength ranking, number of positive signal drugs, and high-risk drug distribution, suggesting that we may need to pay more attention to the liver injury risk of antineoplastic agents in clinical practice.

Delandistrogene moxeparvovec is currently the only commercially approved gene therapy for Duchenne muscular dystrophy (DMD). Herein, we report real-world data of 11 ambulatory patients with DMD, ages 4-6, treated with commercial delandistrogene moxeparvovec. Patients were prospectively and uniformly monitored for 1 year post-gene transfer for safety and motor outcomes. Nine patients experienced 15 treatment-related toxicities, and 4 required escalation of corticosteroids. Side effects included gastrointestinal symptoms (n = 7), liver enzyme abnormalities (n = 4), acute liver injury (n = 2), and troponin I elevations (n = 3). In both patients with acute liver injury, troponin I elevations occurred in close temporal association beginning 8-9 weeks post-gene transfer and were responsive to corticosteroids. The clinical courses of these two patients were at least partially consistent with a cellular immune response to the adeno-associated viral vector (AAV) capsid. Troponin I elevations were asymptomatic and without acute functional changes on echocardiogram. The cohort had improvements in year 1 motor function assessments relative to baseline, including a statistically significant median 4-point increase in North Star Ambulatory Assessment score; however, important confounding factors, e.g., baseline corticosteroid use, limit interpretation and will be important to control for in future real-world datasets. Additional follow-up is required to determine long-term safety and motor outcomes, with unclear generalizability of our results.