@article{59b9b698089a4d60aa390e62aa2e2745,
title = "Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy",
abstract = "Background: Duchenne muscular dystrophy (DMD) is a rare, genetic disease caused by mutations in the DMD gene resulting in an absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, has been shown to increase endogenous dystrophin levels. Herein, long-term (>2 years) functional outcomes in viltolarsen treated patients were compared to a matched historical control group. Objective: To evaluate long-term efficacy and safety of the anti-sense oligonucleotide viltolarsen in the treatment of patients with DMD amenable to exon 53 skipping therapy. Methods: This trial (NCT03167255) is the extension of a previously published 24-week trial in North America (NCT02740972) that examined dystrophin levels, timed function tests compared to a matched historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study, CINRG DNHS), and safety in boys 4 to < 10 years (N = 16) with DMD amenable to exon 53 skipping who were treated with viltolarsen. Both groups were treated with glucocorticoids. All 16 participants elected to enroll in this long-term trial (up to 192 weeks) to continue evaluation of motor function and safety. Results: Time to stand from supine and time to run/walk 10 meters showed stabilization from baseline through week 109 for viltolarsen-treated participants whereas the historical control group showed decline (statistically significant differences for multiple timepoints). Safety was similar to that observed in the previous 24-week trial, which was predominantly mild. There have been no treatment-related serious adverse events and no discontinuations. Conclusions: Based on these results at over 2 years, viltolarsen can be a new treatment option for patients with DMD amenable to exon 53 skipping.",
keywords = "Duchenne muscular dystrophy, clinical efficacy, dystrophin, exon skipping, viltepso, viltolarsen",
author = "Clemens, {Paula R.} and Rao, {Vamshi K.} and Connolly, {Anne M.} and Harper, {Amy D.} and Mah, {Jean K.} and McDonald, {Craig M.} and Smith, {Edward C.} and Zaidman, {Craig M.} and Tomoyuki Nakagawa and Hoffman, {Eric P.}",
note = "Funding Information: f. Dr McDonald has received grants from NS Pharma during the conduct of the study as well as personal fees from Avidity Biosciences, Astellas, Capricor Therapeutics, Catabasis Pharmaceuticals, Edgewise Thera-peutics, Entrada Therapeutics, Epirium Bio, FibroGen, Italfarmaco, Pfizer, PTC Therapeu-tics, Roche, Santhera Pharmaceuticals, Solid Biosciences, and Sarepta Therapeutics outside the submitted work. Funding Information: The CINRG Duchenne Natural History Study (DNHS) was supported by grants H133B031118 and H133B090001 from US Department of Education and National Institute on Disability, Independent Living, and Rehabilitation Research; grant W81XWH-12-1-0417 from the US Department of Defense; grant R01AR061875 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and grants from the Parent Project Muscular Dystrophy. The viltolarsen treatment study was funded by NS Pharma. Funding Information: h. Dr Zaidman has received grant support from Biogen and Novartis outside the submitted work. Funding Information: Writing and editorial support were provided by Marilyn G. Stearns, MD; and Steven D. Stockton, Jr., MS, PhD; from PRI Healthcare Solutions, and were funded by NS Pharma. Funding Information: e. Dr Mah has received grants from NS Pharma during the conduct of the study as well as personal fees from PTC Therapeutics, Biogen and Roche and grants from PTC Therapeutics, Pfizer, Roche, Sarepta Therapeu-tics, Italfarmaco, Novartis, Biogen, ReveraGen BioPharma, Catabasis Pharmaceuticals, Sanofi-Genzyme, and Alberta Children{\textquoteright}s Hospital Foundation outside the submitted work. Funding Information: Rock, PTC Therapeutics, Sarepta Therapeutics, France Foundation, and MDA outside the sub-mitted work. Dr Connolly has received grants from the Washington University School of Medicine and TRiNDS during the conduct of the study as well as grants from Sarepta Therapeutics, AveXis, and Fibrogen and personal fees from Sarepta Therapeutics, Scholar Rock, Genentech-Roche, Dyne Therapeutics, and Edgewise Therapeutics outside the submitted work. Dr Harper has received grants from NS Pharma, Italfarmaco, ReveraGen BioPharma, Cataba-sis Pharmaceuticals, Astellas Pharmaceuticals, MLBio, AveXis, CSL Behring, Teva Pharma-ceutical Industries, Novartis, National Institutes of Health, and US Centers for Disease Control and Prevention. Funding Information: b. Dr Rao has received grants and personal fees from NS Pharma during the conduct of the study and nonfinancial support from Ann and Robert H. Lurie Children{\textquoteright}s Hospital of Chicago dur-ing the conduct of the study as well as personal fees from Biogen, Avexis/Novartis, Capri-cor, Regenxbio, Genentech-Roche, Scholar Publisher Copyright: {\textcopyright} 2022-The authors. Published by IOS Press.",
year = "2022",
doi = "10.3233/JND-220811",
language = "English",
volume = "9",
pages = "493--501",
journal = "Journal of Neuromuscular Diseases",
issn = "2214-3599",
number = "4",
}