Vamorolone versus placebo and prednisone in Duchenne muscular dystrophy: 24-week double blind trial VBP15-004


Clinical Trials

Poster Number: 48


Eric Hoffman, PhD, AGADA Biosciences Inc., Paula R. Clemens, MD, University of Pittsburgh School of Medicine, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA, Seth Perlman, MD, Seattle Childrens, Edward Smith, MD, Duke University Hospital, Iain Horrocks, MD, Richard Finkel, MD, St. Jude Children’s Research Hospital, Memphis, TN, USA., Jean Mah, MD, University of Calgary, Nicolas Deconinck, MD, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des E, Nathalie Goemans, MD, UZ Leuven, Jana Haberlova, MD, Volker Straub, MD, PhD, John Walton Muscular Dystrophy Research Centre and Newcastle Hospitals NHS Foundation Trust, UK, Amy Harper, MD, VCU Health, Perry Sheih, MD, University of California, Los Angeles, David Geffen School of Medicine, Liesbeth de Waele, MD, Diana Castro, MD, University of Texas Southwestern, Dallas, TX, USA., Michele Yang, MD, Monique Ryan, Murdoch Children's Research Institute, Craig McDonald, MD, UC Davis Health, Mar Tulinius, MD, Queen Silvia Children’s Hospital, Gothenburg, Sweden., Richard Webster, MD, The Children’s Hospital at Westmead, Sydney, Australia., Hugh McMillan, MD, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada, Nancy Kuntz, MD, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, USA., Giovanniu Baranello, MD, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK., Stefan Spinty, MD, Alder Hey Children's Hospital, Liverpool, UK, Anne-Marie Childs, MD, Annie Sbrocchi, MD, Kathryn Selby, MD, Children's & Wowen's Health Centre of BC, Yoram Nevo, MD, Juan Vilchez, MD, Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe,Valencia, Spain, Andres Nascimento-Osorio, MD, Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona, Spain, Erik Niks, MD, Leiden University Medical Center, Imelda de Groot, MD, Radboud University Medical Center, Marina Katsalouli, Agia Sophia Children's Hospital, Michela Guglieri, MD, John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle upon Tyne, UK., CINRG and VBP15-004 Investigator

Duchenne muscular dystrophy is an X-linked recessive neuromuscular disorder caused by loss of dystrophin in muscle tissues. Vamorolone is a dissociative steroidal anti-inflammatory drug that changes structure/activity relationships with the glucocorticoid receptor. Previous open label studies of vamorolone have suggested retention of efficacy with reduced safety concerns of corticosteroids.
Steroid-naïve boys with genetically confirmed DMD (5·4±0·9 years; n=121) were randomized in a double-blind, placebo- and prednisone-controlled, Phase 2b (dose-finding) efficacy and safety trial of vamorolone. The primary end point was time to stand from supine velocity (6·0 mg/kg/day vamorolone vs. placebo). Hierarchical testing was used for secondary end points (time to stand velocity, six-minute walk test, and time to run/walk 10 meters velocity at both 6·0 and 2·0 mg/kg/day dose groups).
Vamorolone-treated groups showed improvements in motor function tests over the 24-week treatment period. The trial met the primary and first four sequential secondary end points for change from baseline to Week 24 (time to stand velocity: vamorolone 6·0 mg/kg/day vs. placebo p=0·002, 2·0 mg/kg/day vs. placebo p=0·02; 6-minute walk test 6·0 mg/kg/day vs. placebo p=0·003, 2·0 mg/kg/day vs. placebo p=0.009; time to run/walk 10 meters velocity 6·0 vs. placebo p=0·002). Height percentile declined in prednisone-treated, but not vamorolone-treated participants (least square means [standard error] prednisone ?1·61%tile [1·41] vs. vamorolone 6·0 mg/kg/day +3·40%tile [1·55]; p=0·02). Bone turnover markers declined with prednisone treatment but not vamorolone (p<0·001 for all comparisons). All 3 treatment groups led to adrenal insufficiency, but vamorolone 2·0 mg/kg/day less than prednisone (p<0·002).
Vamorolone is an effective and safer alternative to corticosteroids in Duchenne muscular dystrophy.

(Funded by National Institutes of Health NINDS, and European Commission Horizons 2020; NCT03439670).