Vamorolone Safety, Pharmacokinetics, and Exploratory Efficacy in Duchenne Muscular Dystrophy: A Phase II, Nonrandomized, Multiple-Dose Study in 2-<4-Year-Old Boys.

BACKGROUND AND

objectivesVamorolone is a dissociative corticosteroid (CS) approved by the US Food and Drug Administration in 2023 for treating Duchenne muscular dystrophy (DMD). This study evaluated the safety, tolerability, and pharmacokinetics (PK) of vamorolone in young boys with DMD; exploratory objectives included efficacy and patient-reported outcomes.

methodsA 12-week, phase II, open-label, multiple-dose study (VBP15-006) enrolled CS-naive boys with DMD aged 2-<4 years in Canada. Participants received 2 or 6 mg/kg/d oral vamorolone. An ongoing expanded access protocol (EAP) provided longer-term data. Primary end points were the occurrence of treatment-emergent adverse events (TEAEs) and changes from baseline to week 12 in height, weight, and body mass index (BMI); other end points included PK and effects of vamorolone on muscle function.

resultsTwenty boys (mean age [SD] 3.4 [0.39] years) with similar baseline characteristics were enrolled; all completed VBP15-006 and 19 continued to receive vamorolone through EAP Canada. TEAEs were mostly mild, with no deaths, serious TEAEs, or TEAEs leading to drug discontinuation during VBP15-006. TEAEs were more frequent with 6 mg/kg/d vamorolone than with 2 mg/kg/d, with gastrointestinal disorders and infections/infestations, respectively, most reported. Vamorolone use was associated with morning serum cortisol reductions in all patients, more pronounced with 6 mg/kg/d. Stable growth trajectories were observed at both doses throughout VBP15-006 and the EAP Canada follow-up period, with a total median (Q1; Q3) exposure to vamorolone of 2 years (1.7; 2.3). By EAP Canada last visit, 8/19 patients had weight and BMI DISCUSSION: Vamorolone was well tolerated in 2-<4-year-old boys with DMD, with no new safety concerns identified. A dose-dependent PK profile was observed, consistent with previous studies. Exploratory evidence suggested dose-dependent improvements in gross motor function. These findings are consistent with potential therapeutic benefit of vamorolone for young boys with DMD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT05185622 (VBP15-006; clinicaltrials.gov/study/NCT05185622), NCT03863119 (EAP; clinicaltrials.gov/study/NCT03863119). First submitted November 9, 2021. First patient enrolled: March 21, 2022. CLASSIFICATION OF EVIDENCE: The VBP15-006 study provides Class IV evidence that in boys with DMD aged 2-<4 years, 12-week treatment with vamorolone was not associated with serious adverse events or changes in weight, height, or BMI. Gastrointestinal events and infections were the most reported TEAEs.