Results of North Star Ambulatory Assessments (NSAA) in the Phase 3 Ataluren Confirmatory Trial in Patients with Nonsense Mutation Duchenne Muscular Dystrophy (ACT DMD) (S28.002)

Objective: Examine the efficacy of ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) as assessed by the NSAA.Background: Results of the Phase 3, randomized, double-blind, placebo-controlled ACT DMD trial have been reported. The NSAA is a validated functional scale to measure disease progression specifically in ambulant boys with DMD.Design/Methods: ACT DMD enrolled males aged 7-16 years with nmDMD and baseline six-minute walk distance (6MWD) ≥150m and ≤80[percnt]-predicted. Eligible patients were randomized 1:1 to receive ataluren 10, 10, 20 mg/kg or placebo orally three times daily for 48 weeks. A subgroup analysis of patients with baseline 6MWD of 300-400m was pre-specified. The NSAA consists of 17 activities ranging from standing from a chair to jumping. Each activity is scored as 0, 1, or 2; the sum of these 17 scores forms the total score, which is linearized to a 0 (worst)-100 (best) score.Results: The intent-to-treat population of ACT DMD consisted of 228 patients (ataluren, n=114; placebo, n=114). Overall, patients who received ataluren gained a 1.5-point advantage in NSAA observed score compared with patients who received placebo (mean NSAA scores, ataluren: -7.0; placebo: -8.5; p=0.270). In the pre-specified subgroup of 99 patients with baseline 6MWD 300-400m, the advantage conferred by ataluren over placebo increased to 4.5 points (mean observed NSAA scores, ataluren: -5.7; placebo: -10.2; p=0.030).Conclusions: Ataluren is the first drug to demonstrate a benefit to patients with nmDMD compared with placebo as assessed by NSAA scores; this benefit was especially pronounced in the subgroup of patients with baseline 6MWD 300-400m. NSAA results when combined with 6MWD results, provide complementary information on different aspects of motor function in nmDMD patients and further demonstrate the efficacy of ataluren in this patient population. More detailed analysis of NSAA domains will be presented.Supported By: PTC Therapeutics Inc. Disclosure: Dr. Bushby has nothing to disclose. Dr. Kirschner has received research support from ISIS Pharmaceuticals, Biogen, PTC Therapeutics, Eli Lilly and Company, BioMarin, and Novartis. 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. Muntoni has received compensation for activities with Sarepta Therapeutics.