Ataluren Delays Ambulatory Decline in Patients With Duchenne Muscular Dystrophy

Ataluren delays clinically meaningful milestones of genetically confirmed nonsense mutation Duchenne muscular dystrophy (DMD) progression that predict ambulatory decline, according to study results presented at the 2024 American Academy of Neurology (AAN) annual meeting, held from April 13 to 18, 2024, in Denver, Colorado.

Researchers conducted an international, phase 3, randomized, double-blind, placebo-controlled study (Study 041; NCT03179631) to evaluate the effects of ataluren on clinically meaningful milestones in Duchenne muscular dystrophy. The study comprised of a 72-week ataluren trial followed by a 72-week open-label period involving boys with genetically confirmed nonsense mutation Duchenne muscular dystrophy aged 5 years and older with a 6-minute walk distance of 150 m and more. Patients were randomly assigned 1:1 to receive either ataluren or placebo.  The intention to treat (ITT) population comprised boys who received at least 1 dose of study treatment. The primary outcome of interest was decline in 6-minute walk distance over the course of 72 weeks.

In the ITT population (ataluren, n=183; placebo, n=176), ataluren was associated with a reduced risk for persistent 10% and 5% worsening in 6-minute walk distance by 31% (P =.0078) and 30% (P =.0082), respectively, as well as a 30 m decline in 6-minute walk distance by 31% (P =.0067) relative to placebo.

Among the subgroup of patients who had a 300 to 400 m 6-minute walk distance  at baseline, ataluren significantly reduced the risk for persistent 10% and 5% worsening in 6-minute walk distance by 47% (P =.0011) and 42% (P =.0029), respectively, as well as a 30 m decline in 6-minute walk distance by 47% (P =.0009) relative to placebo.

Although there was a reduced risk for 10% persistent worsening 6-minute walk distance in patients treated with ataluren vs placebo in the primary analysis subgroup, it was not statistically significant (P =.0659).

“These results indicate that ataluren delays clinically meaningful milestones of nmDMD [nonsense mutation Duchenne muscular dystrophy] progression that predict ambulatory decline,” the researchers concluded.

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