Feasibility of switch from prednisone to vamorolone in patients with DMD in VBP15-004 study


Clinical Trials

Poster Number: Virtual


Shabir Hasham, MD, Santhera Pharmaceuticals Ltd, Mika Leinonen, MSc, Santhera Pharmaceticals, 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, 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, Marina, Eric Hoffman, PhD, AGADA Biosciences Inc.

Vamorolone is a dissociative steroidal anti-inflammatory drug that seeks to retain efficacy and reduce safety concerns in patients with Duchenne Muscular Dystrophy compared to corticosteroids via changes to structure/activity relationships with the glucocorticoid receptor.

The objective of this analysis is to evaluate the efficacy and safety in patients who switched from prednisone to vamorolone in the second period of the study

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 initiated on vamorolone continued their assigned treatment and those on placebo or prednisone crossed over to treatment with vamorolone 2 or 6 mg/kg/day. Changes in efficacy outcomes were assessed by time to stand velocity (TTSTANDV), 6-minute walk distance (6MWT), 10-meter run/walk velocity (TTRWV), NSAA score and 4-stair climb velocity (TTCLIMBV).

Out of 121 patients, 30 received prednisone during Period 1 followed by vamorolone treatment during Period 2. All 30 completed vamorolone treatment to Week 48. Efficacy was maintained across all functional endpoints after switching from prednisone to vamorolone 6 mg/kg/day. No significant differences were seen at Week 48 in any efficacy endpoints versus patients continuously treated with vamorolone 6 mg/kg/day throughout the study. No serious adverse events were reported after the switch. Annualized rates of adverse events were reduced after the switch from prednisone to vamorolone (all events: 20% reduction, steroid-related events: 40% reduction). Stunting of growth observed with prednisone during Period 1 was reversed during treatment with vamorolone during Period 2.

There was no loss of efficacy after switching from prednisone to vamorolone 6 mg/kg/day. After the switch, the rate of adverse events on vamorolone was reduced compared to that reported on prednisone and stunting of growth reversed.