Sarepta’s DMD Gene Therapy Elevidys Demonstrates Manageable Safety Across 5-Year Timespan
In pooled data from 156 patients, there were no deaths or study discontinuations.
This article originally appeared on our sister site, NeurologyLive®.
Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus ( rAAVrh74) vector-based gene therapy intended to slow progression of Duchenne muscular dystrophy (DMD) through delivery of a microdystrophin transgene, showed consistent safety outcomes across a broad population of patients with the disease. The data, which come from pooled clinical trial results, were recently presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas.1
Patients (n = 156) from 4 clinical trials were included in the pooled analysis—Study 101 (NCT03375164), Study 102 (NCT03769116), ENDEAVOR Cohorts 1-5b (NCT04626674), and EMBARK Part 1 (NCT05096221). The patients had up to 5 years of follow-up as of January 15, 2024. The pooled group had an age range of 3.2 to 20.2 years (mean, 6.7 years) and the mean weight for the group was 24.6 kg (range, 12.5-80.1 kg). Patients who were ambulatory at baseline constituted 95% (n = 148) of the total group.
Treatment-related, treatment-emergent adverse events (TR-TEAEs) were most often observed in the 90 day window after administration of the gene therapy. The most common TR-TEAEs, reported in at least 15% of patients, included vomiting, nausea, decreased appetite, increased glutamate dehydrogenase levels, and upper abdominal pain, according to Jerry Mendell, MD, advisor to the Jerry R. Mendell Center for Gene Therapy, who presented the findings. Notably, spontaneous resolution or resolution after appropriate management was observed for most of these events.
Serious treatment-related AEs were primarily related to the liver—liver abnormalities were seen in 8 events. Rhabdomyolysis (events, n = 4), vomiting (events, n = 3), myocarditis (events, n = 2), immune-mediated myositis (events, n = 2), nausea (events, n = 1), and pyrexia (events, n = 1) constituted other serious AEs.
Across age and disease progression subgroups safety outcomes were consistent, including in ambulatory patients aged 3 years to 7 years (n = 141), ambulatory patients aged 8 years to 13 years (n = 7), and nonambulatory patients aged 9 years to 21 years (n = 8). There were no clinically significant AEs related to complement activation, importantly.
As of January 15, 2024, no deaths or study discontinuations had been reported. The overall safety and tolerability profile of the gene therapy product was deemed manageable, regardless of age, weight, or disease stage. Overall, these findings supported the continued investigation and use of delandistrogene moxeparvovec as a gene therapy option for patients with DMD.
Delandistrogene moxeparvovec, a gene replacement therapy initially granted accelerated approval in June 2023, recently expanded its label to include both ambulatory and nonambulatory patients over 4 years of age. The approval was based on data from 3 clinical trials which included the phase 1/2 SRP-9001-101 (NCT03375164) study, the phase 2 SRP-9001-102 study, and the phase 1 ENDEAVOR study (SRP-9001-103; NCT04626674). Overall, the treatment was approved based on changes in a surrogate end point—the expression of microdystrophin—from several of these different trials.
Although clinical trials reported predictable and manageable safety outcomes, real-world data presented at the 2025 MDA Conference has provided additional insights into the therapy’s tolerability and highlighted rare but serious AEs.2 In a retrospective chart review conducted at the Neuromuscular Clinic at Children’s Health Dallas, 14 patients with confirmed DMD were treated with delandistrogene moxeparvovec between July 2023 and December 2024. The mean age at the time of treatment was 6.5 years, with the oldest patient being 14 years old and nonambulatory. Patients varied in their pretreatment steroid regimens: 6 were steroid-naïve, 6 were on daily steroids, and 2 were on a weekend regimen. All transitioned to high-dose daily steroids post treatment, as recommended by the therapy's label.
Presented by lead author Lauren Hendrix, BSN, RN, CPN, a nurse at Children's Health, mild gastrointestinal AEs were the most commonly reported AEs, which was consistent with the previous clinical trial data. Among the 14 patients, 11 experienced nausea, vomiting, or decreased appetite and mild myalgia was noted in 1 patient.
Serious AEs were rare but significant. One patient experienced acute liver injury, and another developed acute myocarditis—both required hospitalization and were treated with high-dose intravenous steroids. Additionally, 2 patients classified as high-risk because of the presence of late gadolinium enhancement on cardiac MRI underwent more frequent post treatment monitoring.
The findings reinforce the manageable safety profile of delandistrogene moxeparvovec seen in clinical trials, with gastrointestinal AEs remaining the most common. Although, the occurrence of serious events like myocarditis and liver injury underscored the need for continued vigilance and monitoring. Further real-world data may be essential to fully understand the prevalence and management of these potential risks in a broader DMD population.
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