Ataluren Confirmatory Trial in DMD: Effect of Ataluren on Activities of Daily Living in Nonsense Mutation Duchenne Muscular Dystrophy | DuchenneXchange

welcome to DuchenneXchange

- a positively charged Duchenne muscular dystrophy community.
  • join today!
Abstracts & Posters

Ataluren Confirmatory Trial in DMD: Effect of Ataluren on Activities of Daily Living in Nonsense Mutation Duchenne Muscular Dystrophy

key information

source: American Academy of Neurology

year: 2016

authors: Ros Quinlivan, Xiaohui Luo, G. Elfring, Hans Kroger, Peter Riebling, Tuyen Ong, Robert Spiegel, Stuart Peltz, Jan Kirschner

summary/abstract:

Objective:

Evaluate the effect of ataluren on ambulatory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Change in activities of daily living (ADL) was investigated as a secondary endpoint.

 

Background:

Ataluren is the first drug to target the underlying cause of nmDMD, by promoting readthrough of a premature stop codon to produce full-length functional dystrophin. Methods: ACT DMD was a randomized (1:1), double-blind, placebo-controlled Phase 3 study that evaluated ataluren 40 mg/kg/day, administered over 3 doses, vs placebo over 48 weeks. Inclusion/exclusion criteria were designed to enrich for a population with the greatest opportunity to detect a clinical benefit over a 48-week study, while being inclusive enough to enroll an appropriate number of subjects over a feasible time period for an orphan disease. Participants were males 7-16 years of age with a screening six-minute walk distance (6MWD) >=150m and <=80%-predicted. Patients or parents/caregivers reported changes from baseline in physical functioning, general energy level, cognition/school function, emotional/social functioning, and sleep, rated on a Likert scale from 1 (much worse) to 5 (much better), using a DMD-specific survey developed for this study.

 

Results:

230 patients were randomized to ataluren (n=115) or placebo (n=115). Changes in ADL/disease symptoms trended in favor of ataluren versus placebo across all physical functioning categories, including lower- and upper-extremity muscle function. At Week 48, more ataluren- than placebo-treated patients reported improvement (22.2% vs 16.1%, respectively) or lack of progression (55.6% vs 50.9%) in walking and fewer ataluren-treated patients reported worsening in walking (22.2% vs 33.0%). These effects did not reach statistical significance. The same pattern of changes (with smaller group differences) was observed for stair-climbing and upper extremity activities of self-care.

 

Conclusions:

Results indicate a positive clinical effect of ataluren on ADL in boys with nmDMD, expanding the benefit beyond ambulation.

organisation: PTC Therapeutics

read more