Long-term dose-titration experience with vamorolone in subjects with Duchenne muscular dystrophy (DMD) enrolled in Expanded Access Programs


Topic:

Other

Poster Number: P105

Author(s):

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: 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.

Objective: To report experience with vamorolone dose titration in Expanded Access Programs (EAPs).

Methods: Data were collated from patients who had completed studies VBP15-LTE or VBP15-004 and enrolled in 1 of 3 EAPs in the US, Canada, and Israel. Available data were pooled to explore the frequency of dose titration during the EAPs. The EAPs allowed for up- or down-titration of vamorolone as medically warranted.

Results: At EAP baseline, the median age of patients (N=69) was 7.1 years, median height was 117.5 cm, and median weight was 25.8 kg. At the start of the EAPs, most patients were dosed at vamorolone 4 mg/kg/day (44.9%; n=31) or 6 mg/kg/day (39.1%; n=27), with fewer dosed at 2 mg/kg/day (15.9%; n=11). The median duration of vamorolone exposure during the EAPs was 3.3 years with a maximum of 4.9 years. The majority of patients did not change dose, and up- and down-titrations occurred at a similar frequency. Up-titration from 4 to 6 mg/kg/day and down-titration from 6 to 4 mg/kg/day were the most common dose changes, and the least common changes were down-titrations from the higher doses to 2 mg/kg/day. During the EAPs, 16 patients discontinued treatment; most of these were due to withdrawal by either the patient or parent/guardian (n=14), one was due to physician decision, and one was due to an adverse event. By the end of the EAP or treatment cutoff, most patients were dosed at vamorolone 4 mg/kg/day (43.5%; n=30) or 6 mg/kg/day (37.7%; n=26) and fewer were dosed at 2 mg/kg/day (18.8%; n=13).

Conclusions: Long-term experience in the EAPs shows that vamorolone 4 and 6 mg/kg/day are the most frequently used doses and that most patients do not change dose. However, the therapeutic dose range from 2 to 6 mg/kg/day allows physicians to up- or down-titrate dosing based on individual tolerability.