Vamorolone dose-titration in expanded access protocols and its impact on rates of weight change in subjects with Duchenne muscular dystrophy (DMD)


Clinical Trials

Poster Number: M191


Ana de Vera, MD, Santhera Pharmaceuticals, Wido Tilmann, Greg Ball, Raoul Rooman, MD, Santhera Pharmaceuticals, Eric Hoffman, PhD, AGADA Biosciences, Inc., Paula Clemens, MD, University of Pittsburgh, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, VBP15-004 investigators

Background: The recommended dose of vamorolone in children with DMD is 6 mg/kg/day. Doses may be titrated down to as low as 2 mg/kg/day, based on tolerability. Vamorolone is associated with a dose-dependent risk for weight gain, but prior studies have not investigated the impact of dose titration on weight gain. Subjects continued treatment in Expanded Access Programs (EAPs), which allow for up- or down-titration between 2, 4 and 6 mg/kg/day as medically warranted.

Objective: To report experience with vamorolone dose titration in EAPs and the impact of down-titration on weight percentiles.

Methods: Data were collated from subjects who had completed studies VBP15-LTE, VBP15-004 or VBP15-006 and enrolled in one of three EAPs in the USA, Canada and Israel, as of 21 July 2023. Available data were pooled to explore the effect of dose titration on weight changes. Two analysis sets were created. A down-titration set (DTS; N=17) included subjects with ≥3 weight measurements on vamorolone 6 mg/kg/day, followed by ≥3 weight measurements after down-titrating to 4 mg/kg/day. The up-titration analysis set (UTS; N=16) included subjects with ≥3 weight measurements on vamorolone 2 mg/kg/day followed by ≥3 weight measurements after up-titrating to 4 mg/kg/day. Annualised changes in weight percentiles before and after titration were estimated using mixed models.

Results: The median duration of vamorolone exposure in the EAPs (N=99) was 2.1 years with a maximum of 4.4 years. Most subjects were dosed at some point with vamorolone 4 mg/kg/day (58/99 [58.6%]) or 6 mg/kg/day (57/99 [57.6%]), with a smaller proportion dosed at 2 mg/kg/day (21/99 [21.2%]). 14.0% of subjects on 6 mg/kg/day reported adverse events leading to dose reduction, mainly weight gain. In the DTS, the annual rate of change in weight percentiles (95% CI) decreased from 19.0 (7.5, 30.5) during treatment at 6 mg/kg/day to 4.6 (-0.8, 9.9) after down-titration to 4 mg/kg/day. In the UTS, the annual rate of change in weight percentiles (95% CI) remained stable despite the dose increase, changing from 12.4 (0.4, 24.3) during treatment at 2 mg/kg/day to 10.6 (3.8, 17.4) after up-titration to 4 mg/kg/day.

Conclusion: Dose-titration experience in the EAPs showed that down-titration from vamorolone 6 mg/kg/day to 4 mg/kg/day resulted in a reduction of further weight gain. No evidence of an increased risk for weight gain was observed in subjects who up-titrated from 2 mg/kg/day to 4 mg/kg/day.