Safety and Tolerability of Ataluren in a Phase 3 Study of Patients with Nonsense Mutation Duchenne Muscular Dystrophy (P3.164)

Abstract

Objective: Examine the safety/tolerability of ataluren in the Ataluren Confirmatory Trial in Duchenne Muscular Dystrophy (ACT DMD), a randomized, double-blind, placebo-controlled Phase 3 study of patients with nonsense mutation DMD (nmDMD). Background: A randomized, double-blind, placebo-controlled Phase 2b study of ataluren in patients with nmDMD reported that ataluren was generally well tolerated. Design/Methods: In this Phase 3, ACT DMD, multicenter study, males aged 7-16 years with nmDMD, baseline six-minute walk distance (6MWD) ≥150m and ≤80[percnt] of predicted, and steroid use ≥6 months were randomized 1:1 to ataluren 10, 10, 20 mg/kg or placebo orally 3 times daily for 48 weeks. Results: 230 patients were randomized (ataluren, n=115; placebo, n=115). Demographics were well balanced across treatment arms. Overall, 96.1[percnt] of patients completed the 48-week trial, and 97[percnt] of those chose to continue in the extension study. 103 (89.6[percnt]) patients on ataluren and 100 (87.0[percnt]) patients on placebo experienced treatment-emergent adverse events (TEAEs). The most common TEAEs in the ataluren and placebo arms, respectively, were vomiting (22.6[percnt] and 18.3[percnt]), nasopharyngitis (20.9[percnt] and 19.1[percnt]), fall (19.1[percnt] and 17.4[percnt]), headache (18.3[percnt] for both), and cough (16.5[percnt] and 11.3[percnt]). Four patients in each arm had at least 1 serious adverse event (SAEs). In the ataluren arm, these SAEs were pneumonia and bronchiolitis in 1 patient, pneumonia and post-traumatic pain in 1 patient, tendon disorder in 1 patient, and adenoidal and nasal turbinate hypertrophy in 1 patient; none were considered ataluren-related by the investigator. Only 1 patient in each arm discontinued treatment due to TEAEs: 1 patient discontinued ataluren due to Grade 2 constipation considered possibly related to treatment, and 1 patient discontinued placebo due to loss of ambulation. Conclusions: Ataluren was generally well-tolerated by patients with nmDMD, and the spectrum and severity of adverse events was consistent with previous studies. Supported By: PTC Therapeutics Inc.

Disclosure: Dr. Campbell has nothing to disclose. Dr. Shieh has received personal compensation for activities with Grifols, BioMarin Pharmaceutical, Biogen, Sarepta Therapeutics, Marathon Pharmaceuticals, Cytokinetics, Novartis, Catalyst Pharmaceuticals, and PTC Therapeutics. Dr. Sejersen has received personal compensation for activities with PTC Therapeutics, Biomarin, and Biogene. Dr. Luo has received personal compensation for activities with PTC Therapeutics as an employee. Dr. Elfring has received personal compensation for activities with PTC Therapeutics as an employee. Dr. Kroger has received personal compensation for activities with PTC Therapeutics, Inc. as an employee. Dr. Riebling has received personal compensation for activities with PTC Therapeutics, Inc. Dr. Ong has received personal compensation for activities with a pharmaceutical company as an employee. Dr. Spiegel has received personal compensation from PTC Therapeutics. Dr. Peltz has nothing to disclose. Dr. Wong has received personal compensation for market research for drug trials in pediatric neuromuscular disorders.