Journal Article

Adrenal Suppression From Vamorolone and Prednisone in Duchenne Muscular Dystrophy: Results From the Phase 2b Clinical Trial

Rooman, Raoul, Ward, Leanne M, Dang, Utkarsh J, Ahmet, Alexandra, Tobin, Rebecca, Hoffman, Eric P, Clemens, Paula R, Guglieri, Michela

2025

Overview

Abstract Context Vamorolone, a novel “dissociative” steroid, demonstrated similar efficacy in muscle function relative to prednisone 0.75 mg/kg/day but improved linear growth and bone turnover markers in a randomized trial of pediatric Duchenne muscular dystrophy (DMD). Objectives To determine the frequency of adrenal suppression (AS) induced by vamorolone and prednisone in pediatric DMD and to assess cortisol thresholds using a monoclonal antibody immunoassay. Methods Post hoc analysis of cortisol levels was performed on data from a randomized, double-blind, placebo- and prednisone-controlled 24-week trial of vamorolone with a 24-week crossover extension. Morning and ACTH-stimulated cortisol levels were measured using the Elecsys II immunoassay, with AS defined as a stimulated cortisol of <500 nmol/L (“historical threshold”) and <400 nmol/L (“revised threshold”). Results Mean age at enrolment was 5.41 ± 0.86 years (n = 118). At week 24, the proportion of participants with AS using the historical and revised cortisol thresholds, respectively, were as follows: prednisone 0.75 mg/kg/day = 100% (25/25) and 92.0% (23/25); vamorolone 6 mg/kg/day = 95.2% (20/21) and 90.5% (19/21); vamorolone 2 mg/kg/day = 84.2% (16/19) and 47.5% (9/19); and placebo = 20.0% (4/20) and 0% (0/20). Morning and peak ACTH-stimulated cortisol were strongly correlated in steroid-treated boys (Spearman correlation week 48 = 0.83). Conclusion AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone.

• Publisher: Oxford University Press
• Subject: Adrenal Insufficiency - chemically induced / Adrenocorticotropic hormone / Bone growth / Bone turnover / Child / Child, Preschool / Clinical / Clinical trials / Cortisol / Cross-Over Studies / Dosage / Double-Blind Method / Duchenne's muscular dystrophy / Glucocorticoids - adverse effects / Hormones / Humans / Hydrocortisone / Hydrocortisone - blood / Immunoassay / Male / Monoclonal antibodies / Muscular dystrophy / Muscular Dystrophy, Duchenne - blood / Muscular Dystrophy, Duchenne - drug therapy / Pediatrics / Placebos / Prednisone / Prednisone - administration & dosage / Prednisone - adverse effects / Prednisone - therapeutic use / Pregnadienediols - adverse effects / Steroids