Safety, Tolerability, and Efficacy of a Prophylactic Sirolimus Protocol for Patients Receiving Delandistrogene Moxeparvovec-Rokl Gene Therapy.

Delandistrogene moxeparvovec-rokl (DMR) is the only U.S. Food and Drug Administration-approved gene therapy for patients with Duchenne muscular dystrophy (DMD). After reports of two deaths due to acute liver injury (ALI)/acute liver failure, our center began prophylaxis with sirolimus to help prevent ALI. The objective of this study is to report the initial safety, tolerability, and efficacy of sirolimus prophylaxis. The clinical course of patients receiving sirolimus prophylaxis with a target trough of 4-6 ng/mL was retrospectively evaluated and compared with those who did not receive sirolimus. Laboratory testing, particularly gamma glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and total bilirubin, was collected. A Fisher's exact test was used to assess the difference between groups. Twelve patients were started on sirolimus prophylaxis, 10 prior to DMR infusion and 2 within 2 weeks of DMR. The median age at DMR dosing was 11 years old (interquartile range = 8.5-14); 11 patients were ambulatory. No patients experienced a serious adverse event related to sirolimus administration. Seven patients developed elevated triglyceride or cholesterol levels and began omega-3 supplementation. None of the patients receiving sirolimus prophylaxis experienced ALI compared with 3 of the 14 patients (21%) infused prior to implementation of the sirolimus protocol. Sirolimus prophylaxis appears to be safe and well-tolerated in DMD patients receiving DMR. While not statistically significant, these results suggest that further study of sirolimus prophylaxis is warranted.