Patients With DMD Receiving Eteplirsen Show Prolonged Survival, Study Finds

Patients with Duchenne muscular dystrophy (DMD) with exon 51 skip-amenable variants who received eteplirsen (Exondys 51; Sarepta Therapeutics) experienced improved survival compared with the natural history of DMD, according to a study published in Muscle & Nerve.¹

DMD is a genetic condition characterized by alterations of a protein called dystrophin.² Patients with DMD experience progressive muscle loss and weakness that typically begins in early childhood, and patients typically do not survive past young adulthood. However, advances in DMD care are extending life expectancy for these patients.

Eteplirsen, an antisense oligonucleotide, was initially FDA approved in 2016 and marked the first approval of a drug for DMD.³ It is specifically indicated for the treatment of patients with DMD pathogenic gene variants amenable to exon 51 skipping. While DMD is still considered incurable, treatments such as eteplirsen can slow disease progression.¹

“Based on clinical data, eteplirsen has been shown to have a favorable safety profile and to slow disease progression, delaying deterioration of ambulatory and respiratory function compared with variant-matched external controls,” the study authors wrote.

Doctors planning DMD treatment | Image credit: OlegKachura-stock.adobe.com

The retrospective study characterized overall survival in most patients in the US receiving eteplirsen since its approval, as well as contextualized the benefits compared with DMD natural history cohorts. A targeted literature review of studies published through June 30, 2022, was conducted to form a natural history control cohort for contextualization.

The researchers used deidentified data from SareptAssist, a manufacturer-run support program that contains information on most commercially and government-insured patients who have received eteplirsen since its approval. Information on age at treatment initiation, date of eteplirsen initiation, date of discontinuation, date of patient death or last date known to be alive, and previous participation in a selection of trials of eteplirsen were available for each patient.

A total of 579 patients treated with eteplirsen were included in the study, with all patients born between 1985 and 2020. Eteplirsen was initiated at ages ranging from 1 to 35 years, and the mean (SD) age at initiation was 11.9 (6.4) years. Patients received eteplirsen for up to 8.6 years, with a mean (SD) of 3.7 (1.9) years, and 143 patients had participated in a clinical trial of eteplirsen previously.

The total follow-up was 2119 person-years, and median survival was 32.8 years among patients treated with eteplirsen vs 27.4 years in 1224 DMD natural history controls. Those treated with eteplirsen experienced significantly longer survival from treatment initiation compared with age-matched controls (age-adjusted HR, 0.65; 95% CI, 0.44-0.98; P < .05).

Longer exposure to treatment was also linked with improved survival (HR, 0.15; 95% CI, 0.05-0.41; P < .001). Among patients aged 10 to 28 years, a subgroup which has shown a higher likelihood of deaths, patients treated with eteplirsen had a higher probability of survival compared with natural history controls (HR, 0.58; 95% CI, 0.38-0.89), but neither group reached median survival time.

“This study reports overall survival outcomes from a large cohort of patients receiving eteplirsen. Median survival age appeared to be greater when compared with multiple published DMD natural history controls from similar birth cohorts representing the US and other regions,” the authors wrote. “When compared with age-matched DMD [natural history] controls, eteplirsen treatment was associated with a lower hazard of death. Sensitivity analyses of survival that included DMD [natural history] data from different geographic regions yielded similar results.”

The authors addressed several limitations of the study, including that patients who access eteplirsen with health insurance may not be representative of the overall DMD population. The overall treatment exposure was also relatively low, the authors noted, which may limit the identification of survival benefits. Different follow-up lengths across studies may also impact results, they added.

Still, the study provides evidence of survival benefits among patients with DMD receiving eteplirsen.

“The clinical data presented in the current study suggest that eteplirsen may prolong survival in patients with DMD across a wide age range in both unadjusted and treatment initiation age-adjusted analyses,” the authors concluded. “However, acknowledging the rare nature of disease, multiple confounding variables, and evolving standard of care, further analyses should be conducted on survival impact of DMD therapies as more data become available.”

References

1. Iff J, Done N, Tuttle E, et al. Survival among patients receiving eteplirsen for up to 8 years for the treatment of Duchenne muscular dystrophy and contextualization with natural history controls. Muscle Nerve. Published online March 14, 2024. doi:10.1002/mus.28075

2. Duchenne muscular dystrophy (DMD). Muscular Dystrophy Association. Accessed April 25, 2024. https://www.mda.org/disease/duchenne-muscular-dystrophy

3. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. News release. FDA. September 19, 2016. Accessed April 25, 2024. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy