Vamorolone for Duchenne
(2026)Objective
To assess the safety, tolerability, and pharmacokinetics of vamorolone in 7- to <18-year-old boys with Duchenne muscular dystrophy (DMD) who were either corticosteroid (CS)-untreated or switching from prior classic CS treatment, with exploratory efficacy and pharmacodynamic safety biomarkers.
Study Summary
• No negative effect on growth: CS-untreated boys maintained stable linear growth and CS-treated boys showed catch-up growth consistent with serum bone biomarkers (median total vamorolone exposure 1.3 vs 1.7 years)
• Dose-dependent adrenal suppression occurred; 2 boys switched from deflazacort to vamorolone 2 mg/kg/day developed generalized weakness consistent with adrenal insufficiency, and switching to 6 mg/kg/day appeared to mitigate this risk
• Vamorolone showed dose-dependent pharmacokinetics, rapid clearance, and no accumulation; no relevant efficacy changes were seen in either group at either dose
Intervention
Vamorolone 2 or 6 mg/kg/day for 12 weeks, followed by open-label treatment in the EAP Canada expanded access protocol
Inclusion Criteria
Male, 7- to <18 years, genetically confirmed DMD and/or dystrophin deficiency on muscle biopsy, immunity to varicella zoster virus; either CS-untreated (no oral CS for ≥3 months) or on standard-of-care classic CS switching directly to vamorolone
Study Design
Arms: Vamorolone 2 mg/kg/day or 6 mg/kg/day in CS-untreated (n=12) and previously CS-treated/switched (n=22) boys
Patients per Arm: CS-untreated n=12; CS-treated/switched n=22 (per-dose split across 2 and 6 mg/kg/day subgroups not reported in available text)
Outcome
• No growth stunting; CS-treated boys showed catch-up growth, CS-untreated maintained stable linear growth
• Dose-dependent adrenal suppression; adrenal insufficiency in 2 boys switched from deflazacort to 2 mg/kg/day, mitigated by 6 mg/kg/day dosing
• No relevant efficacy changes at either dose; dose-dependent PK with rapid clearance and no accumulation
Bottom Line
Vamorolone demonstrated a consistent safety profile in 7- to <18-year-old boys with DMD with no negative effect on growth (and catch-up growth in previously CS-treated boys). Switching to 6 mg/kg/day rather than 2 mg/kg/day appeared to mitigate the risk of adrenal insufficiency when transitioning from classic corticosteroids.
Major Points
- 34 boys aged 7- to <18 years (12 CS-untreated, 22 CS-treated) all completed the 12-week VBP15-006 study and continued into the EAP Canada expanded access protocol.
- Most treatment-emergent adverse events were mild.
- No negative effect on growth: CS-untreated participants maintained stable linear growth, while previously CS-treated participants exhibited catch-up growth consistent with serum bone biomarkers (median total vamorolone exposure 1.3 years CS-untreated vs 1.7 years CS-treated).
- Some weight gain occurred, especially in CS-untreated participants receiving 6 mg/kg/day.
- Dose-dependent adrenal suppression occurred in both groups; 2 individuals who switched from deflazacort to vamorolone 2 mg/kg/day developed generalized weakness consistent with adrenal insufficiency, and switching to 6 mg/kg/day appeared to mitigate this risk.
- Vamorolone showed dose-dependent pharmacokinetics with rapid clearance and no accumulation.
- No relevant efficacy changes were observed in CS-treated or CS-untreated groups at either dose (exploratory).
Study Design
- Study Type
- Phase II, non-randomized, multiple-cohort, open-label, multiple-dose study followed by expanded access protocol (EAP Canada)
- Randomization
- No
- Blinding
- Open-label
- Sample Size
- 34
- Follow-up
- 12 weeks core study, then ongoing EAP Canada (median total vamorolone exposure 1.3 years CS-untreated, 1.7 years CS-treated; EAP data cut-off May 2025)
- Centers
- 5
- Countries
- Canada
Primary Outcome
Definition: Safety, tolerability, and pharmacokinetics of vamorolone (2 vs 6 mg/kg/day) over 12 weeks of treatment in 7- to <18-year-old boys with DMD
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Most treatment-emergent adverse events mild; all 34 participants completed the study; dose-dependent PK with rapid clearance and no accumulation | - |
Limitations & Criticisms
- Non-randomized, open-label design with no concurrent control arm
- Small sample size (34) with per-dose subgroups too small for definitive comparisons
- Exploratory efficacy assessments only; EAP Canada not designed to assess effectiveness and used pooled, physician-discretion dosing
- Industry-sponsored (Santhera), with several authors employed by the sponsor
Citation
Lochmüller H, et al. Results of a phase II open-label, multiple-dose study of vamorolone (VBP15-006) in 7- to <18-year-old boys with duchenne muscular dystrophy. J Neurol. 2026;273(3):177.