Background: Eteplirsen is indicated to treat Duchenne muscular dystrophy (DMD) with genetic mutations amenable to exon 51 skipping. Previous analyses have shown that eteplirsen is associated with significant and clinically meaningful delays in time to loss of ambulation (LOA). Additional data now allow for more comprehensive analysis of a larger number of eteplirsen-treated patients. Objective: To estimate the treatment benefit of eteplirsen versus standard-of-care (SOC) for time to LOA from birth using a post-hoc analysis of individual patient level data. Methods: Glucocorticoid-treated DMD patients with mutations amenable to exon 51 skipping, receiving eteplirsen or SOC and ambulatory at study baseline were included. Eteplirsen-treated patients (n=118) were drawn from eteplirsen clinical trials, SOC patients (n=113) were drawn from the placebo arm of the DEMAND III trial, and three natural history databases (CINRG, Leuven and Telethon). LOA was defined as a combination of 10m walk/run time ≥30s and/or 6MWD = 0m or inability to complete the test. Kaplan-Meier analyses and a Cox proportional hazards model (adjusted for treatment) were used to compare LOA between groups. A sensitivity analysis included all genotyped CINRG patients who were ambulatory at baseline, excluding skip exon-44 and del_3-7, in the SOC group (n=278). Results: Time to LOA from birth was significantly longer in the eteplirsen treatment group, with an increase in median age at LOA of 2.7 years (15.7 vs 13.0 years for eteplirsen vs SOC) and a hazard ratio of 0.53 (95% CI: 0.30, 0.93; p=0.027). Median age at LOA in the SOC group was similar to that identified in a previous publication of a broader population of patients from CINRG. Results were robust to the inclusion of all genotyped CINRG patients. Conclusion: Time to LOA from birth was significantly longer in patients treated with eteplirsen than with SOC.