Comparative analysis of long-term effectiveness of vamorolone vs standard of care glucocorticoid (SoC GC) treatment in boys with DMD

Topic:

Clinical Trials

Poster Number: 23 S

Author(s):

Craig McDonald, MD, UC Davis Health, Anne-Marie Childs, MD, Leeds Teaching Hospitals NHS Trust, Leeds, UK, Liesbeth De Waele, MD PhD, University Hospitals Leuven, Ekaterina Gresko, physician-biochemist, PhD, Santhera Paramaceuticals, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK , Jana Haberlova, Dr, Charles University and Motol University Hospital, Prague, Czech Republic, Shabir Hasham, MD, Santhera Pharmaceuticals, Pratteln, Switzerland, Marina Katsalouli, MD, St. Sophia’s Children’s Hospital, Athens, Greece, Mika Leinonen, MSc, Santhera Pharmaceuticals, Pratteln, Switzerland, Aki Linden, MSc, Santhera Pharmaceuticals Schweiz AG, Eugenio M. Mercuri, MD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Francesco Muntoni, MD, Dubowitz Neuromuscular Centre, UCL and Great Ormond Street Hospital Trust, London, UK, Yoram Nevo, MD, Tel Aviv University, Tel Aviv and Schneider Children's Med. Center of Israel, Petach Tikva, Israel, Erik Niks, MD, PhD, Leiden University Medical Center, Leiden, Netherlands, Leanne Ward, MD FRCPC, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada

Background: Vamorolone has demonstrated efficacy for the treatment of DMD in short-term studies; however, the long-term durability remains unknown.

Objective: To assess the long-term effectiveness and changes in anthropometric measures in DMD boys treated with vamorolone compared to SoC GCs.

Methods: Corticosteroid-naïve children with DMD who initiated vamorolone between 4-7 years of age as part of VISION-DMD (NCT03439670) and VBP15-002/003/LTE (NCT02760264/NCT02760277/NCT03038399) studies and continued through various access programs until enrolling into GUARDIAN (NCT06713135). Patients had > 1 year of drug exposure and follow-up. Results were compared to pooled data from external studies (FOR-DMD [NCT01603407]; CINRG Duchenne Natural History Study [NCT00468832]) using propensity score matching. Loss of ambulation (LoA) was analysed by time to event (TTE) approach; slope analysis was used for anthropometry.

Results: The mean (SD) baseline age for TTE analysis was 5.8 (1.0) (vamorolone; N=81) and 6.1 (1.2) years (GCs; N=287), and for anthropometric analysis 5.8 (1.0) (vamorolone; N=110) and 5.9 (1.1) years (GCs; N=199). Both vamorolone cohorts had median drug exposures of ~5 years vs ~4.5 years for both SoC-GC cohorts. All drug exposures were daily. Majority of both vamorolone cohorts received 4-6mg/kg/day vamorolone, with exposures of 306 (TTE) and 410 (anthropometric) patient-years and 84 (TTE) and 107 (anthropometric) for 2 mg/kg/day. No statistically significant difference was seen in time from treatment start to LoA between vamorolone and pooled SoC GCs (nor deflazacort or prednisone separately), with Hazard Ratios (HR) of 1.05 (95% CI 0.53; 2.10), p=0.9041; 1.22 (0.57; 2.60), p=0.6544 and 0.92 (0.44; 1.94), p=0.8587. Vamorolone patients maintained normal growth whereas growth stunting (height Z-score < -2.0 SD) was observed on SOC-GCs (p<.0001). There was no difference in increase in BMI Z-scores between vamorolone and SoC-GCs over time or in weight-to-height trajectories. Conclusions: Our results suggest comparable effectiveness of approximately 5 years of vamorolone to SoC-GCs while preserving growth.