Eteplirsen Treatment Significantly Slows Heart Function Decline in Duchenne Muscular Dystrophy

Joel Iff, PharmD, PhD

(Credit: LinkedIn)

According to a recent analysis presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas, findings showed that eteplirsen (Exondys 51; Sarepta Therapeutics) treatment had significantly reduced the decline in left ventricular ejection fraction (LVEF) among patients with Duchenne muscular dystrophy (DMD). This retrospective study suggested that those on the drug experienced slower rates of LVEF decline and were less likely to reach critical LVEF thresholds indicative of worsening heart function.¹

The study analyzed data from eteplirsen clinical trials and matched patients with DMD from natural history studies using propensity score matching. Over an average follow-up of 26.5 months for eteplirsen-treated patients and 69.3 months for controls, eteplirsen-treated patients had significantly lower risks of reaching LVEF thresholds below 55% and 60%. The annual rate of LVEF decline was also substantially slower in the eteplirsen group, with a decrease of –0.66% compared with –1.38% in the control group.

Presented by lead author Joel Iff, PharmD, PhD, executive director, global access, value and evidence, Sarepta Therapeutics, a total of 141 eteplirsen-treated patients and 103 control patients were available for matching. The final analysis included 122 treated patients matched with 122 controls, resulting in 2 distinct cohorts with similar baseline characteristics, including age, LVEF, and treatment exposure. The primary outcome was the risk of reaching critical LVEF thresholds (50%, 55%, 60%), with Cox proportional hazard models used to analyze these risks. The analysis revealed a significantly lower risk in the treated cohort, with hazard ratios of 0.22 (P <.01) for LVEF less than 55% and 0.40 (P <.01) for LVEF less than 60%.

Overall, eteplirsen-treated patients experienced a slower rate of LVEF decline compared with controls (–0.66% vs. –1.38%, P <.01). The results remained consistent across sensitivity analyses, including E-value and restricted mean survival time analyses that evaluated potential bias and geographic imbalances. All told, these findings suggest that eteplirsen may help preserve cardiac function in patients with DMD, offering potential therapeutic benefits beyond its primary role in promoting dystrophin production.

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Following promising results in slowing heart function decline in patients with DMD, eteplirsen continues to show potential in addressing key aspects of the disease. The latest data from the phase 4 EVOLVE study presented at the 2025 MDA Conference revealed that eteplirsen significantly delayed loss of ambulation (LOA), providing further evidence of the drug’s ability to impact the course of DMD in a clinical setting.²

The EVOLVE study, designed to assess eteplirsen’s effects on LOA in routine clinical practice, included 33 eteplirsen-treated patients and 75 external controls from 5 major studies. After adjusting for baseline differences through inverse probability treatment weighting (IPTW), the study reported that the risk of LOA was reduced by 62% in eteplirsen-treated patients. Additionally, the median age at LOA was significantly higher for treated patients (15.3 years) compared with external controls (11.3 years), further underscoring the treatment’s effectiveness.

The study aimed to evaluate the real-world impact of eteplirsen on LOA in patients with exon 51 skip-amenable DMD. Propensity score weighting balanced baseline factors such as age, corticosteroid use, and mobility measures across the 2 groups. The final analysis included 33 treated patients and 75 matched external controls from studies such as CINRG-DNHS and FOR-DMD.

LOA was determined by patient-reported wheelchair use, North Star Ambulatory Assessment (NSAA) scores, and a 10-meter walk/run (10MWR) score of at least 30, validated by the attending physician. Eteplirsen-treated patients experienced a median age of 15.3 years at LOA, significantly later than the 11.3 years in the control group, indicating a delay in disease progression.

The analysis showed a 62% reduction in the risk of LOA for eteplirsen-treated patients (hazard ratio of 0.38, 95% CI, 0.18–0.82; P = .011). By age 15, treated patients had a 36% higher likelihood of remaining ambulant compared with controls. The probability of remaining ambulant was 0.50 for eteplirsen-treated patients, versus just 0.14 for external controls.

The EVOLVE study demonstrated that eteplirsen-treated patients maintained mobility longer than those on standard care, offering a promising treatment option to prolong ambulation and quality of life in DMD. As the evidence continues to grow, eteplirsen’s impact on the disease, both in terms of heart function and mobility, reinforces its potential as a cornerstone in DMD care.

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REFERENCES
1. Iff J, Desguerre I, Liu Y, et al. Association Between Exon-Skipping Therapy With Eteplirsen and Cardiac Outcomes in Duchenne Muscular Dystrophy. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-19. Dallas, TX. Abstract P79
2. Mathews K, Grabich S, Dharmarajan S, et al. Comparative Analysis of Loss of Ambulation in Eteplirsen-Treated Patients With DMD in the EVOLVE Study and Propensity Score–Weighted External Controls. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-19. Dallas, TX. Abstract P103.