Long-term impact of vamorolone on bone health compared to standard of care glucocorticoids (SoC-GC) in boys with Duchenne Muscular Dystrophy (DMD)

Topic:

Clinical Trials

Poster Number: 62 S

Author(s):

Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK , 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, Jana Haberlova, Dr, Charles University and Motol University Hospital, Prague, Czech Republic, Shabir Hasham, MD, Santhera Pharmaceuticals, Pratteln, Switzerland, Jacob Jaremko, MD, University of Alberta, Edmonton, AB, Canada, Marina Katsalouli, MD, St. Sophia’s Children’s Hospital, Athens, Greece, Khaldoun Koujok, MD, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada, Mika Leinonen, MSc, Santhera Pharmaceuticals, Pratteln, Switzerland, Aki Linden, MSc, Santhera Pharmaceuticals Schweiz AG, Laura McAdam, University of Toronto, Toronto, ON, Canada, Craig McDonald, MD, University of California Davis Health, Hugh McMillan, MD, Children's Hospital of Eastern Ontario, 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: Boys with DMD on standard of care glucocorticoids (SoC-GC) have high vertebral fracture (VF) risk and bone age delay.

Objectives: Indirect comparison of VF and bone age delay in DMD boys after long-term treatment with vamorolone vs SoC-GC.

Methods: Baseline data from 37 patients enrolled in GUARDIAN were used for propensity score matching with a SoC-GC cohort (N=60), previously published (Phung K & Ward LM. Osteoporosis Int. 2023 Jan; mostly on daily deflazacort). VF were evaluated on lateral spine X-rays according to the Genant semi-quantitative methodology, the Spinal Deformity Index (SDI) was calculated (sum of the Genant grades), and bone age was evaluated by BoneXpert™ on hand X-rays.

Results: At the time of the X-rays, mean ±SD ages in vamorolone (N=37) and matched GC (N=31) cohorts were 10.9±1.25 and 11.7±1.53 years. Mean drug exposure was 5.2±0.95 years for vamorolone (190.6 patient-years) vs 5.4±2.06 years on SoC-GC (167.5 patient-years). Mean doses at the time of X-ray were 4.89±1.28 mg/kg/day and 0.65±0.21 mg/kg/day for vamorolone and deflazacort, respectively. 3/37 (8.1%) patients had 9 VF on vamorolone vs 13/31 (41.9%) with 30 VF on SoC-GC (Odds Ratio (95%CI) 0.1296 (0.02903, 0.5789), p=0.0082). The mean SDI for subjects with and without VF was lower on vamorolone vs SoC-GC (0.32 vs 1.06). In the vamorolone cohort, the 3 patients with VF had SDI scores of 1, 3 and 8. In SoC-GC cohort, among the 13 patients with VF, 7 had SDI of 1, while the remaining patients had SDIs of 3, 4 (n=3), 5 and 6. Mean bone age delay was 0.8±1.5 years on vamorolone vs 1.6±1.6 years on SoC-GC.

Conclusions: The prevalence of VF was significantly lower with vamorolone compared to SoC-GC after ~5 years of exposure. Patients on vamorolone should continue to be monitored for VF.