Vamorolone is Efficacious at 48 Weeks for Motor Outcomes in Boys With DMD

The efficacy of vamorolone at a dose of 6 mg/kg per day is maintained over 48 weeks in boys with Duchenne muscular dystrophy (DMD). Moreover, bone morbidities associated with prednisone treatment are reversed when patients cross over from prednisone to vamorolone. These are the findings of a study published in Neurology.

Researchers conducted a randomized, double-blind trial (ClinicalTrials.gov Identifier: NCT03439670) at 33 sites in 11 countries between 2018 and 2021 to evaluate whether vamorolone was associated with sustained improvement in motor outcomes through 48 weeks and whether prednisone treatment-related bone morbidities were reversable with vamorolone crossover. Boys with DMD aged between 4 and 7 who were corticosteroid-naïve and had a time to stand from supine of 10 or fewer seconds were eligible for inclusion. Patients were randomly assigned in a 2:2:1:1:1:1 ratio to receive:

• 2 mg/kg vamorolone,
• 6 mg/kg vamorolone,
• 0.75 mg/kg prednisone crossed over to 2 mg/kg vamorolone,
• 0.75 mg/kg prednisone crossed over to 6 mg/kg vamorolone,
• Placebo crossed over to 2 mg/kg vamorolone, or
• Placebo crossed over to 6 mg/kg vamorolone, respectively.

Treatment was received daily for 48 weeks. Crossover occurred at week 24.

Efficacy was assessed via 5 gross motor function outcomes (time to stand from floor velocity, 6-minute walk distance, time to run or walk 10 m velocity, North Star Ambulatory Assessment, and time to climb 4 stairs velocity). Changes over the treatment periods were analyzed using mixed models for repeated measures.

A total of 121 patients enrolled in the study, 112 of whom completed the study. The trial met the primary endpoint for change from baseline to week 24 time to stand velocity for vamorolone at a dose of 6 mg/kg daily vs placebo, as well as the first 4 sequential secondary endpoints.

The improvements observed in all 5 motor function outcomes after 24 weeks of vamorolone treatment at a dose of 6 mg/kg daily were maintained through week 48. The improvement in time to stand from floor velocity demonstrated by vamorolone at a dose of 6 mg/kg daily after 24 weeks (least square mean [LSM], 0.052 rises/second) was maintained at week 48 (LSM, 0.0446 rises/second). Patients who received vamorolone at a dose of 2 mg/kg daily showed improvement at 24 weeks and then maintenance or some decline at 48 weeks across all 5 motor outcomes.

Patients who crossed over to vamorolone at a dose of 6 mg/kg daily from placebo exhibited improvements in all 5 motor outcomes post-crossover.

Patients who crossed over from prednisone to vamorolone at a dose of 6 mg/kg daily maintained improvements achieved with prednisone for all 5 motor outcomes. However, those who crossed over from prednisone to vamorolone at a dose of 2 mg/kg daily exhibited more variability across outcomes, with maintenance benefit for time to stand from floor velocity, 6-minute walk distance, and North Star Ambulatory Assessment, but regression in time to run or walk 10 m velocity and time to climb 4 stairs velocity.

Treatment with vamorolone for 48 weeks demonstrated normal growth trajectories in patients, with no significant dose-dependent differences.

Patients who crossed over from prednisone to vamorolone, prednisone exhibited slowing of growth velocities during the prednisone treatment period and reversal of growth trajectories (height z score) during the vamorolone at a dose of 6 mg/kg daily treatment period (LSM, 0.228; 95% CI, 0.0157-0.44; P =.036).

Compared with prednisone crossover to vamorolone at a dose of 6 mg/kg daily, vamorolone at a dose of 6 mg/kg daily throughout the entire 48-week treatment period demonstrated positive catchup growth; however, those who crossed over from prednisone to vamorolone treatment had lower height z scores at 48 weeks (LSM, 0.067; 95% CI, -0.149 to 0.284; P =0.53).

Vamorolone was generally well-tolerated at both dose levels through 48 weeks with a dose-dependent profile of adverse events.

This study was limited by missing data due to the COVID-19 pandemic.

“This study provides Class I evidence that for boys with DMD [Duchenne MD], the efficacy of vamorolone at a dose of 6 mg/kg/d [day] was maintained over 48 weeks,” the researchers concluded.

Disclosures: This research was supported by ReveraGen BioPharma. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.