Growth velocity changes in boys with Duchenne muscular dystrophy (DMD) treated with vamorolone, prednisone, deflazacort, and placebo

Topic:

Other

Poster Number: P110

Author(s):

Stanley Iyadurai, MSc, PhD, MD, FAAN, Catalyst Pharmaceuticals, Ana de Vera, MD, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Aki Linden, Santhera Pharmaceuticals (Switzerland) Ltd, Pratteln, Switzerland, Paula R Clemens, MD, University of Pittsburgh, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK, Keri Kasun, PharmD, Catalyst Pharmaceuticals, Raymond Czaja, Pharm D, Catalyst Pharmaceuticals, Eric Hoffman, PhD, Reveragen BioPharma, Rockville, Maryland, United States of America

Background: Children with DMD are on average shorter than the general population by the age of 5 years, and daily dosing with prednisone (PDN) or deflazacort (DFZ) leads to further growth stunting (Bello L, et al. 2015 PMID: 26311750; Stimpson G, et al. 2022 PMID: 35073949). Vamorolone (Vam), a novel drug with a chemical structure distinct from classic corticosteroids, is approved for the treatment of patients with DMD in the US (patients aged ≥2 years) and Europe (patients aged ≥4 years).

Objective: The aim of this post hoc analysis was to compare growth velocities between Vam-, PDN-, and placebo (PBO)-treated participants over 24 weeks from the VISION-DMD study and in long-term studies of participants treated with Vam vs an external comparator cohort (FOR-DMD) treated with PDN and DFZ.

Methods: In this cross-study comparison, data were analyzed from 2 randomized, double-blind studies (FOR-DMD and VISION-DMD) and 1 open-label study (VBP15-LTE). Three comparisons were estimated: 1) 24-week within-trial comparison in VISION-DMD, comparing PBO, PDN, Vam 2 mg/kg/day and Vam 6 mg/kg/day; 2) 48-week comparison between VISION-DMD and FOR-DMD, comparing DFZ, PDN, Vam 2 mg/kg/day and Vam 6 mg/kg/day; 3) 2.5-year comparison between VBP15-LTE and FOR-DMD, comparing DFZ, PDN, and Vam 2-6 mg/kg/day. Mean growth velocity changes and intercohort differences were calculated using linear regression. Analysis of covariance was performed with baseline height and age as covariates per FDA 2007 guidance.

Results: In the 24-week analysis (VISION-DMD), patients receiving PDN, Vam 2 mg/kg/day, or Vam 6 mg/kg/day had similar growth velocities compared with patients receiving PBO. Patients receiving Vam 6 mg/kg/day had a significantly higher growth velocity compared with those receiving PDN (P=0.005). In the 48-week analysis of VISION-DMD and FOR-DMD, patients receiving Vam 2 or 6 mg/kg/day had significantly higher growth velocities compared with patients receiving DFZ (P<0.0001, both cohorts) or PDN (P<0.0001, both cohorts). In the 2.5-year analysis of VBP15-LTE and FOR-DMD, patients treated with Vam 2-6 mg/kg/day had significantly higher growth velocities than the PDN- and DFZ-treated cohorts (Vam 2-6 mg/kg/day vs DFZ: P<0.001; Vam 2-6 mg/kg/day vs PDN: P<0.0001). Conclusion: The results of this post hoc analysis suggest that Vam does not appear to impair linear growth as do PDN or DFZ.