Delay in Duchenne Muscular Dystrophy Progression with Eteplirsen: Longer Time to Loss of Ambulation versus Standard of Care

Background/Purpose: Eteplirsen is indicated in the United States to treat Duchenne muscular dystrophy (DMD) with exon 51 skip-amenable mutations. Here we estimate treatment benefit of eteplirsen versus standard of care (SOC) for time to loss of ambulation (LOA) from birth using post hoc analyses of individual patient data.

Methods: Glucocorticoid-treated exon 51 skip-amenable patients with DMD, receiving eteplirsen or SOC and ambulatory at baseline, were included. Eteplirsen-treated patients (n = 118) were drawn from eteplirsen clinical trials; SOC patients (n = 113) were drawn from the DEMAND III trial placebo arm and natural history databases (CINRG, Leuven, Telethon). Kaplan–Meier analyses and Cox proportional hazards model compared groups for LOA, defined as combined 10-m walk/run ≥30 s and/or 6-m walk distance = 0 m or unable to complete. Sensitivity analysis included all genotyped, baseline-ambulatory CINRG patients, excluding skip exon-44 and del_3-7, in the SOC group (n = 290).

Results: Time to LOA from birth was significantly longer in eteplirsen-treated patients, with an increase in median age at LOA of 2.7 years (eteplirsen, 15.7 years; SOC, 13.0 years) and hazard ratio of 0.56 (95% CI: 0.32, 0.99; p = 0.046). Median age at LOA in SOC patients was similar to a previous publication of a broader population from CINRG. Results were robust to the inclusion of all genotyped CINRG patients.

Conclusion: Time to LOA from birth was significantly longer in eteplirsen-treated patients versus SOC patients.

Funding

This study was funded by Sarepta Therapeutics, Inc.

Conflict of Interest

J.I., B.H., and A.M.-Y. are employees of Sarepta Therapeutics, Inc, and may own stock/options in the company. G.B. was an employee of DRG Abacus at the time of the study. A.P. is an employee of Zedediah Consulting and partner of DRG Abacus. H.G.-D. is the cofounder of TRiNDS, LLC. E.H. reports consulting fees (Sarepta Therapeutics, Inc). C.M. reports consulting (Astellas/Mitobridge, Bristol-Myers Squibb, Capricor, Catabasis Pharmaceuticals, Edgewise Therapeutics, Eli Lilly, Epirium Bio [formerly Cardero Therapeutics], Gilead, Halo Therapeutics, Italfarmaco, Novartis, Pfizer, Prosensa, PTC Pharmaceuticals, Santhera Pharmaceuticals, and Sarepta Therapeutics, Inc); research funding, principal investigator, and speaking fees (Sarepta Therapeutics, Inc).

^*Presenting on behalf of the authors.

Publication History

Article published online:
28 October 2021