Efficacy and safety of vamorolone during 48-week treatment in patients with Duchenne Muscular Dystrophy (DMD) in VBP15-004 study

Topic:

Clinical Trials

Poster Number: Virtual

Author(s):

Mika Leinonen, MSc, Santhera Pharmaceticals, Shabir Hasham, MD, Santhera Pharmaceuticals Ltd, Michela Guglieri, MD, John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle upon Tyne, UK., 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 Shieh, 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, Dr, 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, Eric Hoffman, PhD, AGADA Biosciences Inc.

Background
Vamorolone is a dissociative steroidal anti-inflammatory drug that seeks to retain efficacy and reduce safety concerns in patients with DMD compared to corticosteroids via changes to structure/activity relationships with the glucocorticoid receptor.
Objectives
The objective of this analysis is to evaluate efficacy and safety of continuous 48-week vamorolone treatment.
Methods
VISION-DMD (VBP15-004) is a 48-week randomized, double-blind study consisting of two periods. During Period 1, 121 patients were randomized 1:1:1:1 to vamorolone 2 or 6 mg/kg/day, prednisone 0.75 mg/kg/day or placebo for 24 weeks. During Period 2, patients continued their initial vamorolone dose or crossed over to vamorolone 2 or 6 mg/kg/day. Changes from baseline to Week 48 in efficacy outcomes; time to stand velocity (TTSTANDV), 6-minute walk distance (6MWT), 10-meter run/walk velocity (TTRWV), NSAA score and 4-stair climb velocity (TTCLIMBV) were analyzed with MMRM.
Results
Of the 121 patients, 56 received vamorolone during both Period 1 and 2. Two of 56 patients discontinued treatment during Period 2 (1 adverse event, 1 consent withdrawn). For vamorolone 6 mg/kg/day, efficacy was maintained or further improved from Week 24 to Week 48, whilst for vamorolone 2 mg/kg/day, efficacy was maintained in some efficacy endpoints but not all. Differences between dose levels were seen in TTSTAND (p=0.001), 6MWT (p=0.047) and TTCLIMB (p=0.031), while not in TTRW (p=0.375) or NSAA (p=0.602). Three serious adverse events were reported during the 48 weeks: perforated appendicitis (2 mg/kg/day), asthma (6 mg/kg/day) and viral gastroenteritis (6 mg/kg/day), all considered unrelated to vamorolone. Stunting of growth was not seen and body mass index stabilized after an initial increase during the first 24 weeks.
Conclusions
Efficacy of vamorolone 6 mg/kg was maintained throughout 48 weeks across all outcome measures, whilst only across some measures for 2mg/kg/day. Vamorolone treatment was generally well tolerated on both dose levels throughout 48 weeks.