Eteplirsen Treatment Linked to Slower Cardiac Decline in DMD

Eteplirsen may significantly delay cardiac deterioration in patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping, according to a retrospective study presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.1 

Eteplirsen was the first drug approved to treat patients with DMD based on data showing an increase in skeletal muscle dystrophin expression in patients with confirmed mutation of the dystrophin gene amenable to exon 51 skipping.2 However, data on its impact on cardiac function are lacking, the authors of the new study explained.1

None of the eteplirsen-treated patients reached an LVEF below 50% compared with 22.1% of patients in the control group. | Image credit: inthasone - stock.adobe.com

“This study is the first to demonstrate significant change in measured cardiac function with an innovative therapy that aims to increase dystrophin expression, suggesting clinically meaningful multi-year delays in reaching cardiomyopathy milestones for treated patients,” the authors wrote.

The new analysis examined the risk of reaching left ventricular ejection fraction (LVEF) thresholds indicative of cardiac function decline, as well as the annual rate of decline in cardiac function based on LVEF in 122 patients treated with eteplirsen vs 122 propensity-matched natural history controls with DMD amenable to exon 51 skipping. Data on patients with DMD were collected from Study 201 (NCT01396239), Study 202 (NCT01540409), Study 203 (NCT02420379), Study 204 (NCT02286947), and Study 301 (NCT02255552); natural history control data were obtained from the Cooperative International Neuromuscular Research Group DMD Natural History Study (CINRG-DNHS; NCT00468832), a Prospective Natural History Study of Progression of Subjects with Duchenne Muscular Dystrophy (PRO-DMD-01; NCT01753804), and the French DMD Heart Registry (NCT03443115).

The mean durations of follow-up were 26.5 months and 69.3 months in the DMD and control groups, respectively, and the LVEF thresholds assessed were below 50%, 55%, and 60%. Time-to-event analysis was performed using Kaplan-Meier curves, and trajectory analysis was conducted via linear mixed-effects models. The impact of eteplirsen on the risk of reaching LVEF decline thresholds was assessed with Cox proportional hazard models.

None of the eteplirsen-treated patients reached an LVEF below 50% compared with 22.1% of patients in the control group. The proportion of eteplirsen-treated patients who reached the other LVEF thresholds was also smaller, with 3.3% of treated patients vs 27.1% of controls reaching an LVEF below 55% and 10.7% of treated patients vs 49.2% of controls reaching an LVEF below 60%.

The HR for time to the first LVEF below 55% event was 0.22 (95% CI, 0.07-0.66; P < .01) among eteplirsen-treated patients relative to matched controls, and the HR for time to the first LVEF below 60% was 0.40 (95% CI, 0.22-0.76; P < .01) among eteplirsen-treated patients vs matched controls. The annual rate of LVEF decline was also significantly slower among eteplirsen-treated patients (–0.66% percentage points per year) vs controls (–1.38% percentage points per year).

The authors noted that data from multiple studies with varied data sources were used, but validation analyses for potential sources of bias, including a restricted mean survival time analysis, also suggested that patients treated with eteplirsen had a lower risk of reaching LVEF thresholds vs natural history controls. A sensitivity analysis using alternate propensity score matching also showed consistent results.

“All results consistently indicated a positive association between eteplirsen and significantly lower risk of LVEF decline for patients with DMD, including the post-matching time-to-event and trajectory analysis with adjustment for key cardiac prognostic factors,” the authors concluded.

References

1. Iff, Desguerre, Liu, et al. Association between exon-skipping therapy with eteplirsen and cardiac outcomes in Duchenne muscular dystrophy. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Poster P79.

2. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. News release. FDA. September 19, 2016. Accessed April 10, 2025. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy