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Background <p>Vamorolone is a dissociative glucocorticoid receptor agonist for treating Duchenne muscular dystrophy (DMD). The VBP15-006 study assessed vamorolone safety, tolerability, and pharmacokinetics in 2- to &lt; 4 and 7- to &lt; 18-year-old boys with DMD. Results for 7- to &lt; 18-year-old boys, either corticosteroid (CS)-untreated or switching from prior CS treatment, are reported here. Exploratory objectives included efficacy and pharmacodynamic biomarkers related to safety.</p> Methods <p>In this phase II, open-label, multiple-dose study, participants received 2 or 6&#xa0;mg/kg/day vamorolone for 12&#xa0;weeks, followed by treatment in an expanded access protocol (EAP Canada).</p> Results <p>34 participants (12 CS-untreated, 22 CS-treated) aged 7- to &lt; 18&#xa0;years were enrolled. Most treatment-emergent adverse events were mild. All 34 participants completed VBP15-006 and entered EAP Canada. During EAP Canada, CS-untreated participants maintained stable linear growth, while CS-treated participants exhibited catch-up growth consistent with serum bone biomarkers (median total vamorolone exposure 1.3 and 1.7&#xa0;years, respectively). Some weight gain occurred, especially in CS-untreated participants receiving 6&#xa0;mg/kg/day. Dose-dependent adrenal suppression occurred in CS-untreated and CS-treated participants; 2 individuals who switched from deflazacort to vamorolone 2&#xa0;mg/kg/day had generalized weakness consistent with adrenal insufficiency. Vamorolone showed dose-dependent pharmacokinetics, rapid clearance, and no accumulation. There were no relevant efficacy changes in CS-treated and CS-untreated groups at either dose.</p> Conclusions <p>Vamorolone demonstrated a consistent safety profile in 7- to &lt; 18-year-old boys with DMD. Switching to 6&#xa0;mg/kg/day vamorolone appeared to mitigate adrenal insufficiency risk. There was no negative effect on growth, and catch-up growth occurred in previously CS-treated individuals switching to vamorolone.</p> Trial registration <p>ClinicalTrials.gov: NCT05185622, NCT03863119. First submitted 09-11-2021.</p>

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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

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  • 发表日期：

    2026年3月3日

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  • Hanns Lochmüller,
  • Hernan Gonorazky,
  • Elisa Nigro,
  • Jean K. Mah,
  • Alberto Alemán,
  • Amanda Yaworski,
  • Maryam Oskoui,
  • Anne Marie Sbrocchi,
  • Kathryn Selby,
  • Ana de Vera,
  • Laura McAdam,
  • Ekaterina Gresko,
  • Aki Linden,
  • Catherine Dutreix,
  • Eric P. Hoffman

摘要

Background

Vamorolone is a dissociative glucocorticoid receptor agonist for treating Duchenne muscular dystrophy (DMD). The VBP15-006 study assessed vamorolone safety, tolerability, and pharmacokinetics in 2- to < 4 and 7- to < 18-year-old boys with DMD. Results for 7- to < 18-year-old boys, either corticosteroid (CS)-untreated or switching from prior CS treatment, are reported here. Exploratory objectives included efficacy and pharmacodynamic biomarkers related to safety.

Methods

In this phase II, open-label, multiple-dose study, participants received 2 or 6 mg/kg/day vamorolone for 12 weeks, followed by treatment in an expanded access protocol (EAP Canada).

Results

34 participants (12 CS-untreated, 22 CS-treated) aged 7- to < 18 years were enrolled. Most treatment-emergent adverse events were mild. All 34 participants completed VBP15-006 and entered EAP Canada. During EAP Canada, CS-untreated participants maintained stable linear growth, while CS-treated participants exhibited catch-up growth consistent with serum bone biomarkers (median total vamorolone exposure 1.3 and 1.7 years, respectively). Some weight gain occurred, especially in CS-untreated participants receiving 6 mg/kg/day. Dose-dependent adrenal suppression occurred in CS-untreated and CS-treated participants; 2 individuals who switched from deflazacort to vamorolone 2 mg/kg/day had generalized weakness consistent with adrenal insufficiency. Vamorolone showed dose-dependent pharmacokinetics, rapid clearance, and no accumulation. There were no relevant efficacy changes in CS-treated and CS-untreated groups at either dose.

Conclusions

Vamorolone demonstrated a consistent safety profile in 7- to < 18-year-old boys with DMD. Switching to 6 mg/kg/day vamorolone appeared to mitigate adrenal insufficiency risk. There was no negative effect on growth, and catch-up growth occurred in previously CS-treated individuals switching to vamorolone.

Trial registration

ClinicalTrials.gov: NCT05185622, NCT03863119. First submitted 09-11-2021.