Eteplirsen

Mercuri E, et al. Neuromuscular Disorders, 2023, 33(6), 476-483.

Eteplirsen targets the underlying genetic mutation in Duchenne muscular dystrophy (DMD) patients amenable to exon 51 skipping. Previously studied in boys aged 4 years and older, eteplirsen has demonstrated efficacy in slowing pulmonary and ambulatory decline. A recent clinical trial expanded its evaluation to younger boys aged 6-48 months, assessing its safety, tolerability, and pharmacokinetics in this demographic.
This open-label, multicenter study involved 15 boys divided into two cohorts (aged 24-48 months, n = 9; aged 6 to < 24 months, n = 6). Participants received weekly intravenous doses of eteplirsen ranging from 2 to 30 mg/kg during a 10-week dose-escalation period, followed by 30 mg/kg for up to 96 weeks. The study's primary endpoint was safety, while pharmacokinetics served as a secondary measure.
All participants completed the study without discontinuation, deaths, or signs of kidney toxicity. Eteplirsen was well tolerated, with adverse events primarily mild and including pyrexia, cough, and gastrointestinal symptoms. Pharmacokinetic analysis confirmed consistency across age groups and alignment with prior findings in older boys. These results validate the safety and tolerability of eteplirsen at the approved 30 mg/kg dose for boys as young as six months.