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Abstract Details

Ataluren Preserves Upper Limb Function in nmDMD Patients from Study 041, a Phase 3 Placebo-Controlled Trial, and the STRIDE Registry
Child Neurology and Developmental Neurology
S34 - Child Neurology and Developmental Neurology 2 (2:24 PM-2:36 PM)
008

DMD is a severe neuromuscular disorder caused by a lack of functional dystrophin. Ataluren promotes readthrough of an in-frame premature stop codon to produce full-length dystrophin and is indicated for the treatment of patients with nmDMD. Study 041 (NCT03179631) is a phase 3, double-blind, placebo-controlled 72-week trial. The STRIDE Registry (NCT02369731) is an ongoing, long-term, real-world evidence study.

To assess performance of upper limb (PUL) function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) receiving ataluren plus standard of care (SoC) in Study 041 (NCT03179631) and in the STRIDE Registry (NCT02369731).

In Study 041, boys with nmDMD aged ≥5 years, on a stable corticosteroid regimen, and with a 6-minute walk distance (6MWD) ≥150m were randomized 1:1, ataluren:placebo. The intention-to-treat (ITT) population comprised randomized boys who received at least one dose of study treatment (N=359; mean age 8.1 years); a key subgroup included those with baseline 300–400m 6MWD (n=169). STRIDE patients were propensity-score matched to patients receiving SoC alone in CINRG DNHS (NCT00468832), yielding a comparable population (N=261). Kaplan-Meier analyses estimated age at loss of upper limb function.

Least-squares mean PUL total score change from baseline to week 72 (by MMRM analysis) numerically favored ataluren versus placebo (0.44, p=0.1059) in the Study 041 ITT population and was significant in the 300–400m 6MWD subgroup (1.02, p=0.0165).

In matched STRIDE versus CINRG patients (mean last assessment age, 13.1 versus 14.6), ataluren preserved hand-to-mouth function by 3.4 years (p=0.0046) as assessed by entry level items of PUL versus Brooke Scale, respectively. Median age at loss of overhead reach numerically favored STRIDE, consistent with the overall trend (15.8 versus 12.6; p=0.2872). Median age at loss of distal hand function was non-estimable for STRIDE patients.  

These results indicate that ataluren may help preserve upper limb function in patients with advanced nmDMD.

Authors/Disclosures
Vinay Penematsa
PRESENTER
Vinay Penematsa has nothing to disclose.
Craig McDonald, MD (UC Davis Dept. of PM&R) 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.
Eugenio Mercuri Eugenio Mercuri 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, Santhera, PTC, Pfizer, Roche, Biogen, Avexis Novartis, Scholar Rock, Cytokinetics. Eugenio Mercuri has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sarepta, Santhera, PTC, Pfizer, Roche, Biogen, Avexis Novartis. The institution of Eugenio Mercuri has received research support from biogen.
Francesco Muntoni, MD (UCL Institute of Child Health) Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Muntoni has received research support from European Commission. The institution of Dr. Muntoni has received research support from Medical Research Council. The institution of Dr. Muntoni has received research support from Biogen. The institution of Dr. Muntoni has received research support from Muscular Dystrophy UK. The institution of Dr. Muntoni has received research support from MDA USA. The institution of Dr. Muntoni has received research support from Sarepta. The institution of Dr. Muntoni has received research support from Association Francoise Myopathies. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving as a Clinical expert with UK NICE Committee.
Heather Gordish-Dressman Heather Gordish-Dressman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AGADA BioSciences. Heather Gordish-Dressman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TRiNDS, LLC. Heather Gordish-Dressman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rejuvenate Bio. An immediate family member of Heather Gordish-Dressman has received intellectual property interests from a discovery or technology relating to health care. Heather Gordish-Dressman has received personal compensation in the range of $500-$4,999 for serving as a TACT Advisory Board Reviewer with TREAT-NMD.
Lauren Morgenroth (TRiNDS, LLC) Ms. Morgenroth has received personal compensation for serving as an employee of TRiNDS. Ms. Morgenroth has stock in TRiNDS.
Maria Bernadete Resende No disclosure on file
Shuizhen Zhou, MD, PhD (Children's Hospital, Fudan University) No disclosure on file
Mathukumalli Lakshmi Neeharika, MD,MBBS,Other (NIZAMS INSTITUTE OF MEDICAL SCIENCES) Dr. Neeharika has nothing to disclose.
Kazuhiro Haginoya, MD (Miyagi Children'S Hospital) Dr. Haginoya has nothing to disclose.
Leigh Ramos-Platt, MD (USC/Children'S Hospital of Los Angeles) Dr. Ramos-Platt has received personal compensation for serving as an employee of MDA. Dr. Ramos-Platt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. The institution of Dr. Ramos-Platt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Ramos-Platt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cure sma.
Paula Williams, Other (PTC Therapeutics, Inc.) Mrs. Williams has nothing to disclose.
Connie Chou Connie Chou has stock in PTC Therapeutics.
Min Lin, PhD (PTC Therapeutics, Inc.) Dr. Lin has received personal compensation for serving as an employee of PTC Therapeutics.
Shelley Yvonne Johnson, Other (PTC Therapeutics Pharmaceutical company) Ms. Johnson has received personal compensation for serving as an employee of PTC Therapeutics Inc. Ms. Johnson has stock in PTC Therapeutics.
Karyn Koladicz, MD (PTC Therapeutics) Dr. Koladicz has received personal compensation for serving as an employee of PTC Therapeutics.
Nicholas Mastrandrea (Edgewise Therapeutics) Nick Mastrandrea has received personal compensation for serving as an employee of PTC Therapeutics. Nick Mastrandrea has stock in PTC Therapeutics.
Christian Werner Christian Werner has received personal compensation for serving as an employee of PTC Therapeutics .
Panayiota Trifillis 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.