Muscle function, linear growth, and bone health during 30 months of vamorolone, prednisone, and deflazacort treatment for Duchenne muscular dystrophy: a comparative study
Leanne M Ward, Stefan Jackowski, Utkarsh J Dang, Maya Scharke B Comm, Jacob L Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Hugh J McMillan, Kerry Siminoski, Mika Leinonen, Raoul Rooman, Shabir Hasham, Paula R Clemens, Michela Guglieri, Eric P HoffmanAbstract
Corticosteroids are standard of care to slow disease progression in Duchenne muscular dystrophy (DMD) despite impaired growth and increased fracture risk. Vamorolone, a dissociative corticosteroid approved for DMD, showed stable growth and serum bone turnover markers in the 48-week VISION-DMD study. We compared muscle function and bone health from the non-randomized, open-label, 30-month Phase 2a VBP15-002/003/LTE trials (NCT02760264/NCT02760277/NCT03038399) in treatment-naive boys with DMD, aged 4 to <7 years at baseline, with data from matched corticosteroids-treated boys from FOR-DMD (NCT01603407). Motor function by slope-of-change analysis was evaluated for vamorolone 2–6 mg/kg/d through 30 months compared with propensity score-matched boys from FOR-DMD who received daily prednisone (starting dosage 0.75 mg/kg/d) or deflazacort (0.9 mg/kg/d) for 36 months. Anthropometric and bone assessments were performed in boys on vamorolone for 30 months, including those who received lower dosages during VBP15-002/003 (0.25/0.75 mg/kg/d for 6 months). Vertebral fracture (VF) prevalence was compared with baseline-matched FOR-DMD data. Thirty-month vamorolone VF results were adjusted to approximate expected fracture prevalence at 36 months. All slope-of-change motor function comparisons between vamorolone (N=22) and prednisone (N=32) or deflazacort (N=34) groups yielded no significant differences (p>0.05). Thirty-month height z-scores remained stable from baseline for vamorolone (N=36; +0.078 least-squares-mean change) and decreased from baseline for prednisone (N=27, –0.668; change versus vamorolone: p<0.0001 mixed models for repeat measures) and deflazacort (N=28, –0.928; change versus vamorolone: p<0.0001). VF prevalence on vamorolone (8 VF in 5/39 boys [12.8%]) was ~50% lower than prednisone (13 VF in 7/27 boys [25.9%]) and deflazacort (19 VF in 8/28 boys [28.6%]). Compared with prednisone and deflazacort, vamorolone demonstrated similar motor function efficacy with significantly fewer VF and preserved growth.