Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study
| العنوان: | Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study |
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| المؤلفون: | Jean K. Mah, Heather Gordish-Dressman, Diana Castro, Nancy L. Kuntz, Utkarsh J. Dang, Laurie S. Conklin, Dnhs Investigators, Jesse M. Damsker, Monique M. Ryan, Paula R. Clemens, Maya Shimony, Phil Shale, Eric P. Hoffman, Mar Tulinius, Richard Webster, Laurel J Mengle-Gaw, Michela Guglieri, Mark Jaros, Laurie Kerchner, Richard S. Finkel, Antonio Arrieta, Edward C. Smith, Craig M. McDonald, Yoram Nevo, Benjamin D Schwartz, Laura Hagerty, Lauren P. Morgenroth |
| المصدر: | PLoS Medicine PLoS Medicine, Vol 17, Iss 9, p e1003222 (2020) |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Heredity, Genetic Linkage, Physiology, Health Care Providers, Duchenne Muscular Dystrophy, Walking, 030204 cardiovascular system & hematology, Weight Gain, Steroid Therapy, Muscular Dystrophies, law.invention, Medical Conditions, Electronics Engineering, 0302 clinical medicine, Randomized controlled trial, Adrenal Cortex Hormones, law, Prednisone, Medicine and Health Sciences, Medical Personnel, 030212 general & internal medicine, Child, Pregnadienediols, Pharmaceutics, General Medicine, Professions, Treatment Outcome, Neurology, Physiological Parameters, X-Linked Traits, Sex Linkage, Research Design, Child, Preschool, Comparators, Ambulatory, Disease Progression, Medicine, Engineering and Technology, medicine.symptom, Research Article, medicine.drug, medicine.medical_specialty, Clinical Research Design, Corticosteroid Therapy, Motor Activity, Research and Analysis Methods, 03 medical and health sciences, Drug Therapy, Physicians, Internal medicine, Genetics, medicine, Humans, Adverse effect, Glucocorticoids, Clinical Genetics, Biological Locomotion, business.industry, Body Weight, Biology and Life Sciences, Interim analysis, Health Care, Muscular Dystrophy, Duchenne, Deflazacort, Clinical trial, People and Places, Population Groupings, Adverse Events, Electronics, business, Weight gain |
| الوصف: | Background Treatment with corticosteroids is recommended for Duchenne muscular dystrophy (DMD) patients to slow the progression of weakness. However, chronic corticosteroid treatment causes significant morbidities. Vamorolone is a first-in-class anti-inflammatory investigational drug that has shown evidence of efficacy in DMD after 24 weeks of treatment at 2.0 or 6.0 mg/kg/day. Here, open-label efficacy and safety experience of vamorolone was evaluated over a period of 18 months in trial participants with DMD. Methods and findings A multicenter, open-label, 24-week trial (VBP15-003) with a 24-month long-term extension (VBP15-LTE) was conducted by the Cooperative International Neuromuscular Research Group (CINRG) and evaluated drug-related effects of vamorolone on motor outcomes and corticosteroid-associated safety concerns. The study was carried out in Canada, US, UK, Australia, Sweden, and Israel, from 2016 to 2019. This report covers the initial 24-week trial and the first 12 months of the VBP15-LTE trial (total treatment period 18 months). DMD trial participants (males, 4 to In an interim analysis of a multi-center open-label study, Edward Smith and colleagues investigate motor outcomes and adverse events in patients with Duchenne muscular dystrophy treated with the novel anti-inflammatory drug vamorolone. Author summary Why was this study done? The standard-of-care pharmacological management of Duchenne muscular dystrophy (DMD) is high-dose corticosteroids (prednisone or deflazacort; about 0.5 to 0.9 mg/kg/day), but this treatment is associated with safety concerns. Vamorolone is a first-in-class steroidal drug that aims to retain or improve efficacy of corticosteroids, while decreasing safety concerns. Twenty-four-week treatment of DMD with vamorolone has been reported to show dose-responsive improvements in motor outcomes, but longer-term treatment and comparative safety profiles to corticosteroids have not been previously reported. What did the researchers do and find? Participants with DMD completing the 24-week dose-ranging study of vamorolone (VBP15-003; n = 46) were offered transition to standard of care (prednisone or deflazacort) or continued treatment with vamorolone with enrollment into a 2-year long-term extension study (VBP15-LTE). All participants (46/46) opted to continue treatment with vamorolone and enrolled in VBP15-LTE. We report data from the midpoint of the 2-year VBP15-LTE study (total of 18 months of vamorolone treatment in VBP15-003 + VBP15-LTE). All measures of efficacy (5 motor outcome tests) showed significant improvements from baseline to 18 months of vamorolone treatment by paired intragroup analyses. Three motor outcome tests could be compared to group-matched corticosteroid-naïve external comparators, and 2 showed significant vamorolone-associated improvement. Vamorolone treatment did not result in stunting of growth, as seen with prednisone and deflazacort. Vamorolone treatment showed fewer physician-reported adverse events (such as behavior change, hirsutism, and Cushingoid appearance) than these drugs. What do these findings mean? Vamorolone holds promise as a replacement for corticosteroid standard of care (prednisone and deflazacort) in DMD. Limitations of the study include the open-label design and use of external comparators. |
| تدمد: | 1549-1676 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6c75b6d44d74183b16be3be6a55e6b4cTest https://doi.org/10.1371/journal.pmed.1003222Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6c75b6d44d74183b16be3be6a55e6b4c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15491676 |
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