In patients with Duchenne muscular dystrophy (DMD), treatment with eteplirsen — a type of antisense oligonucleotide that promotes dystrophin production by restoring the translation reading frame of the DMD gene — is associated with statistically significant, clinically meaningful attenuation in the percentage of predicted forced vital capacity (FVC%p).

Recognizing that pulmonary decline is a major issue in individuals with DMD, researchers sought to evaluate the effect of eteplirsen treatment, as derived from newly available data sources, on pulmonary function over time in patients with DMD.

In this post hoc analysis, researchers compared the FVC%p and projected time with pulmonary function milestones in patients with DMD and exon 51 skip-amenable mutations being treated with eteplirsen. Overall, 113 participants fulfilled the inclusion criteria and were included in the main analysis. Of the patients treated with eteplirsen, 20 were enrolled in Study 204 (ClinicalTrials.gov Identifier: NCT02286947) and 52 were enrolled in Study 301 (ClinicalTrials.gov Identifier: NCT02255552). Of the patients who received standard of care (SoC), 20 were enrolled in Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS; ClinicalTrials.gov Identifier: NCT00468832) and 21 were enrolled in DEMAND III (ClinicalTrials.gov identifier: NCT01254019).


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Since mainly nonambulatory patients were included in Study 204 and only ambulatory patients were enrolled in Study 301, those in the former study were, on average, older, taller, and weighed more at baseline than did those in the latter study. Further, participants from Study 204, on average, required more time to complete the 10-meter walk test and had lower FVC%p. Patients from DEMAND III were slightly younger and had better pulmonary function than those from CINRG-DNHS.

Per results of the study, the average yearly rate of FVC%p decline among patients treated with eteplirsen was estimated to be 3.47% — a statistically significant attenuation from the rate of estimated rate of decline of 5.95% in the SoC participants (P =.0001).

Based on linear extrapolations of the model-estimated decline in FVC%p, the attenuation in FVC%p decline among those treated with eteplirsen corresponded to a delay of 5.72 years in time to requiring continuous ventilation, 3.31 years in time to requiring nighttime ventilation, and 2.11 years in time to requiring a cough-assisted device, compared with patients who received SoC.

Several limitations of the present study should be noted. To begin, a national history study — CINRG-DNHS — was included in the analysis, which used prespecified criteria regarding age and glucocorticoid treatment status, rather than randomized control group comparisons. Sensitivity analyses that utilized both CINRG-DNHS and DEMAND-III placebo-arm participants imply that the results were robust to a group of patients who received SoC from natural study and clinical trial settings.

“The attenuation of FVC%p decline suggests that eteplirsen-treated patients had statistically significant and clinically meaningful attenuations in pulmonary decline compared with SoC patients,” the researchers stated.

They concluded that the decline in FVC%p reported with eteplirsen treatment in the current analysis “corresponded to an estimated delay of approximately 2 to 6 years to reach critical pulmonary milestones when compared with SoC patients.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

This article originally appeared on Neurology Advisor