Sensitivity analyses of time to LOA

In the first sensitivity analysis, information from case manager polls was used for the two patients who did not participate in Study 405 and were censored for follow up at the end of Study 202 in the main analysis. One patient was assumed to lose ambulation after the study completion at the date recorded by the case manager, and a second patient was assumed to remain ambulatory until the end of Study 405, when he was censored for follow-up.

In the second sensitivity analysis, time from birth to LOA was analyzed instead of time from baseline. Although this analysis can be subject to bias, as patients were not treated with eteplirsen since birth, it is a commonly performed analysis in DMD studies when data on baseline prognostic factors are not available.

In the third sensitivity analysis, the assumption that LOA occurred in the midpoint of the interval of uncertainty for patients with imprecisely recorded date of LOA. The date of LOA was alternatively assumed to be at the earliest date of that interval (lower bound) or at the latest date of that interval (upper bound). For example, for a patient with recorded date of LOA of August 2017, the lower bound was August 1, 2017, the midpoint was August 16, 2017, and the upper bound was August 31, 2017.

In the fourth sensitivity analysis, the SOC group was expanded to include patients from the CINRG DNHS. These patients were much younger and had better ambulatory function at baseline compared to eteplirsen-treated patients analyzed here, and thus were not included in the main analyses. The CINRG DNHS patients were included in the sensitivity analysis if they had an exon-51 skip amenable mutation, were ambulatory and treated with corticosteroids, and had 6MWT values available at baseline (study entry). The definition of LOA in CINRG DNHS is identical to that used in Study 405, i.e. full-time wheelchair use. Time to LOA was compared between eteplirsen-treated patients and this expanded SOC group.