Vamorolone for Duchenne Muscular Dystrophy Shows Better Safety Profile Than Other Corticosteroids

Utkarsh Dang, PhD

Data from a recent study (VBP15-LTE; NCT03038399) suggest that vamorolone for the treatment of Duchenne muscular dystrophy (DMD) is not associated with typical safety concerns of corticosteroid treatments, such as slowing of linear growth, insulin resistance, and decreases in osteocalcin.

These findings were presented at the Muscular Dystrophy Association’s (MDA) Scientific and Clinical Conference 2021, March 15-18, by Utkarsh Dang, PhD, assistant professor, Health Outcomes and Administrative Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University.

“The continued use of corticosteroids has been limited by the side effects and a key challenge is how to manage these safety concerns. Moreover, as opposed to the traditional corticosteroids in use, which are prednisone and deflazacort vamorolone is a first-class dissociative steroidal product which dissociates efficacy from safety, the way it does this is by a single change in contact site with a new corticoid receptor,” Dang said during his presentation.

Dang and colleagues found that earlier initiation of high-dose vamorolone treatment delayed decline of motor function compared to patients initiated at lower doses despite being up-titrated to higher doses 6 months later. Motor functions were assessed on time to stand from supine and 6-minute walk tests.

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Participants under the age of 5 years initiated on higher doses showed better clinical outcomes compared to those initially treated at after 5 years of age or with lower doses. Subgroup analyses of patients stratified to the 5-year age cutoff confirmed findings in many outcome measures, indicating a disease modifying effect.

Previously published open-label dose-finding studies investigated doses of 0.25 mg/kg up to 6.0 mg/kg per day of vamorolone, formerly known as VBP15. Doses of 2.0 mg/kg and 6.0 mg/kg per day showed significant motor function improvement over 24 weeks in 48 patients with DMD that were steroid-naïve at entry (age range, 4-7 years). All 46 patients that completed the dose-finding studies (VBP15-002; NCT02760264; VBP15-003; NCT02760277) continued vamorolone, enrolled in the 2-year study, and dose-escalated to either 2.0 mg/kg or 6.0 mg/kg per day. 

Interim analyses at 18 months showed continued improvements of motor outcomes with vamorolone treatment at 2.0 mg/kg or 6.0 mg/kg per day. Researchers observed fewer adverse events (AEs) compared to published studies of corticosteroid treatment. AEs were consistent with results seen in the 18-month interim analysis, with 12 patients (26.1%) experienced weight increase and 2 (4.3%) experienced Cushing syndrome. No evidence of stunted growth was seen.

Of the 46 patients enrolled in the study, 3 discontinued due to participation in other trials, 1 due to study burden, and 1 due to loss of muscle strength. Half the patients were initiated at high doses of 2.0 or 6.0 mg/kg per day and maintained this dosage throughout the study. The other half were initiated at lower doses of 0.25 or 0.75 mg/kg per day and were up-titrated to the higher dosages after 6 months.

“In summary, vamorolone was generally found to be safe and well-tolerated. Improvements from baseline were seen in study participants younger than 5, in disease stability for the study participants during the 30-month follow up treatment period. These data provide evidence of the safety and clinical benefit of a long-term treatment of DMD,” Dang concluded the presentation.

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REFERENCE

Dang U, Clemens P, Gordish-Dressman H, et al. 2.5-years of vamorolone treatment in Duchenne muscular dystrophy: Results of an open label long-term extension. Presented at MDA Clinical and Scientific Conference 2021; March 15–18. Poster 47.