<h3>Objective:</h3> To describe the efficacy and safety results from the placebo-controlled phase of Study 041 (NCT03179631). <h3>Background:</h3> Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by a lack of functional dystrophin. Ataluren promotes read through of an in-frame premature stop codon to produce full-length dystrophin and is indicated for the treatment of patients with nonsense mutation (nm) DMD. Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week ataluren trial in patients with nmDMD followed by a 72-week open-label period. <h3>Design/Methods:</h3> Boys with nmDMD aged ≥5 years, on corticosteroids, and with a 6-minute walk distance (6MWD) ≥150m were eligible. The primary objective was to determine ataluren’s effect on ambulatory function, assessed by the 6-minute walk test. Boys were randomized 1:1 to ataluren:placebo. The intention-to-treat (ITT) population comprised randomized boys who received ≥1 dose of study treatment. Predefined subgroups included boys aged ≥7 to ≤16 years with ≥300m 6MWD and ≥5s stand from supine (primary) and boys with 300–400m 6MWD. <h3>Results:</h3> Ataluren and placebo groups in the ITT population and key subgroups were balanced according to enrolment age, baseline 6MWD, corticosteroid use and time to stand from supine. Significant differences in mean 6MWD change from baseline and rate of change favored ataluren in the ITT population (14.4m; 0.20m/week; <i>p</i>=0.0248) and 300–400m 6MWD subgroup (24.2m; 0.34m/week; <i>p</i>=0.0310), representing a 21% and 30% slowing of the decline rate in 6MWD in these groups, respectively. There were significant treatment benefits in time to 10% worsening of 6MWD. The number of ITT patients who lost ambulation receiving placebo was almost double that of those receiving ataluren. Ataluren was well tolerated, had no probable drug-related serious adverse events (AEs), and AE frequency (85.3%) was similar to placebo (84.7%). <h3>Conclusions:</h3> Study 041 confirms ataluren’s favorable risk-benefit as shown in previous clinical and real-world evidence studies. <b>Disclosure:</b> Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. McDonald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Capricor Therapeutics. Dr. McDonald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Catabasis. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epirium Bio. Dr. McDonald has received personal compensation in the range of $0-$499 for serving as a Consultant for Italfarmaco. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Santhera Pharmaceuticals. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis Pharmaceuticals. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Santhera Pharmaceuticals. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Santhera Pharmaceuticals. The institution of Dr. McDonald has received research support from Astellas. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Catabasis. The institution of Dr. McDonald has received research support from Epirium Bio. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from Pfizer. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from NIDILRR. The institution of Dr. McDonald has received research support from Department of Defense. The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH. Dr. Wu has nothing to disclose. Prof. Gulati has nothing to disclose. Hirofumi Komaki has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Nippon Shinyaku. Hirofumi Komaki has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. The institution of Hirofumi Komaki has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC therapeutics Inc. Hirofumi Komaki has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Chugai . Rosa Escobar Cedillo has nothing to disclose. Anna Kostera-Pruszczyk has nothing to disclose. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Roche. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for PTC Therapeutics. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for PTC Therapeutics. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Jong-Hee Chae has nothing to disclose. Dr. Jong has nothing to disclose. Dr. Karachunski has nothing to disclose. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ML Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epic Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Armatus . Dr. Statland has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity . Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum Therapeutics. Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Statland has received research support from NIH. The institution of Dr. Statland has received research support from FSHD Society. The institution of Dr. Statland has received research support from Friends of FSH Research. The institution of Dr. Statland has received research support from FSHD Canada. The institution of Dr. Statland has received research support from MDA. Dr. Lorentzos has nothing to disclose. Vinay Penematsa has nothing to disclose. Connie Chou has stock in PTC Therapeutics. Dr. Lin has received personal compensation for serving as an employee of PTC Therapeutics. Christian Werner has nothing to disclose. Panayiota Trifillis has received personal compensation for serving as an employee of PTC Therapeutics. Panayiota Trifillis has received stock or an ownership interest from PTC Therapeutics, Inc.. Panayiota Trifillis has received intellectual property interests from a discovery or technology relating to health care. Dr. Gordon has received personal compensation for serving as an employee of PTC Therapeutics. Dr. Koladicz has received personal compensation for serving as an employee of PTC Therapeutics. Nick Mastrandrea has received personal compensation for serving as an employee of PTC Therapeutics. Nick Mastrandrea has stock in PTC Therapeutics. Matthew Klein has nothing to disclose.