Craig McDonald, MDCraig McDonald, MD
Data that were accepted to the American Academy of Neurology (AAN) 2020 Annual Meeting revealed that treatment with eteplirsen (Exondys 51; Sarepta Pharmaceuticals) is associated with a significant reduction in pulmonary decline based on forced vital capacity % predicted (FVC%p) and to the need for continuous ventilation in patients with Duchenne muscular dystrophy (DMD).1

Compared with patients who received standard of care (SoC), eteplirsen-treated patients experienced a statistically significant attenuation in the FVC%p decline (annual rate of decline of 5.96% vs 3.82%, respectively; P <.01).

Senior author Craig McDonald, MD, professor and chair in the department of physical medicine and rehabilitation at the University of California, Davis, and colleagues compared temporal patterns of FVC%p and projected time to continuous ventilation in patients with DMD with exon 51 skippable mutations receiving eteplirsen versus SoC. The study population included 20 patients from Study 204 and 42 patients from Study 301, a subsequently larger efficacy study, who were treated with eteplirsen, as well as an additional 20 controls drawn from the Cooperative International Neuromuscular Research Group (CINRG) database.

A mixed effects model with repeated measures was used to evaluate the impact of eteplirsen on decline in FVC%p, which included glucocorticoid-treated patients between 10 to 18 years.
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The mixed effects model used FVC%p as the response variable, eteplirsen versus control as the treatment group, age (at visit), the interaction between treatment group and age as the fixed effects, and patient as a random effect. Time to continuous ventilation was predicted using a linear extrapolation of the model that estimated decline in FVC%p from average readings observed in patients age 10 to 10.5 years old treated with glucocorticoids in the specific.

Based on an average starting FVC%p of –­77.82% at age 10, the results showed a decline in FVC%p for eteplirsen was associated with a delay of ­­approximately 4.5 years in time to needing continuous ventilation compared with patients treated with SoC; a clinically meaningful delay.

The FDA approved eteplirsen for the treatment of patients with DMD in September 2016. At the time, it was the first drug approved for DMD, and is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.2

Earlier on in its pipeline, the drug was granted orphan drug designation, as well as priority review status and fast track designation. Eteplirsen was also approved under the accelerated approval pathway, which provided earlier patient access while other ongoing trials continued.

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1. Iff J, Gerrits C, Birk E, et al. Delays in progression of Duchenne muscular dystrophy with Eteplirsen treatment: attenuation of pulmonary function decline and projected freedom from continuous ventilation. Neurology. 2020;94(15 Suppl):1398.
2. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy [news release]. FDA. Published September 19, 2016. Accessed May 11, 2020.