2.5-years of vamorolone treatment in Duchenne Muscular Dystrophy: Results of an open label long-term extension

Clinical Trials
Utkarsh Dang PhD, Paula Clemens MD, Heather Gordish-Dressman PhD, Eric Hoffman PhD, Benjamin Schwartz MD, PhD, Laurel Mengle-Gaw PhD, Mika Leinonen PhD, Edward Smith MD, Diana Castro MD, Craig McDonald MD, Nancy Kuntz MD, PhD, Richard Finkel MD, Mar Tulinius MD, Yoram Nevo MD, Monique Ryan MD, Richard Webster MD, John van den Anker MD, PhD, Laurie Conklin MD, Leanne Ward MD, Jesse Damsker PhD, Michela Guglieri MD, Cooperative International Neuromuscular Research Group , Jean Mah MD
1. Binghamton University, 2. University of Pittsburgh, 4. Binghamton University, 7. Santhera Pharmaceuticals, 8. Department of Pediatrics, Duke University School of Medicine, 9. Dept of Pediatrics and Neurology, Univ of Texas Southwestern Medical Center, Dallas, Texas, USA, 10. University of California Davis, 11. Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois, USA, 12. Translational Neuroscience Program, St. Jude Children's Research Hospital, Memphis, TN, US, 13. University of Gothenburg, Sweden, 15. Department of Neurology, Royal Children’s Hospital, 21. John Walton Muscular Dystrophy Research Centre, Newcastle University

Vamorolone is a first-in-class steroidal anti-inflammatory drug with novel structure/activity relationships with glucocorticoid and mineralocorticoid receptor targets compared to deflazacort or prednisone. Published open-label dose-finding studies (0.25–6.0 mg/kg/day) in DMD showed significant motor function improvement over 24 weeks for 2.0 and 6.0 mg/kg/day dose groups (n=48; age 4 to <7 years, steroid naïve at entry). All participants completing VBP15-003 (n=46) chose to continue vamorolone and enrolled in a 2-year extension study, and dose-escalated to either 2.0 or 6.0 mg/kg/day (VBP15-LTE). A published interim analysis (18-month treatment period) showed continued significant improvement of all motor outcomes with vamorolone treatment (2.0+6.0 mg/kg/day), and less side effects compared to published studies of corticosteroid treatment. Here, we present findings at the completion of VBP-LTE (2.5 years treatment). Five of 46 patients discontinued the study due to participation to other trials (3), study burden (1) or loss of muscle strength (1). 23/46 subjects were initiated at high dose (2.0 or 6.0 mg/kg/day) and maintained until end of follow-up. Remaining 23/46 were initiated at lower doses (0.25 or 0.75 mg/kg/day) and up-titrated to the higher doses after >6-months which was maintained throughout the remaining study period. Earlier initiation of high dose vamorolone treatment delayed decline of motor function compared to patients who were initiated at lower doses despite being up-titrated to higher doses 6 months later. Younger subjects (<5 years old) who were initiated on higher doses showed better clinical outcomes compared to those initially treated at a later age or with lower doses. Stratification of participants by baseline age (<5 years, >5 years) showed consistent results within both strata for many outcome measures, indicating a disease modifying effect. Vamorolone treatment was not associated with typical safety concerns of corticosteroid treatment (slowing of linear growth, insulin resistance, decreases in osteocalcin).