Vamorolone is an effective treatment for Duchenne muscular dystrophy (DMD) among boys and may be a safer alternative to prednisone, according to a randomized clinical trial published in JAMA Neurology.
The X-linking disorder DMD affects one in 3600 to 9300 newborn boys and is typically treated with corticosteroids such as prednisone. This treatment delays loss of ambulation but its long-term use has adverse effects such as stunting growth, mood disturbances, and adrenal insufficiency, among others. As there is an unmet clinical need for safer treatment options, researchers sought to evaluate the safety of vamorolone, a dissociative steroidal anti-inflammatory drug.
The randomized, double-blind, placebo- and prednisone-controlled trial (ClinicalTrials.gov Identifier: NCT03439670) included boys aged less than 7 years with DMD who were recruited at 33 sites in 11 countries between June 2018 and February 2021. The study population comprised boys aged mean 5.4 (standard deviation [SD], 0.9) years and 82.9% were White. The trial comprised 2 24-week periods, in which participants were randomized in a 1:1:1:1 ratio to receive placebo (n=28), 0.75 mg/kg daily prednisone (n=31), 2 mg/kg daily vamorolone (n=30), or 6 mg/kg daily vamorolone (n=28) for 24 weeks. In the second 24-week period, the placebo and prednisone groups crossed over to vamorolone. Safety and efficacy were evaluated.
The primary outcome was time to stand from supine (TTSTAND) velocity in the vamorolone 6 mg/kg per day group vs placebo.
From baseline to week 24, TTSTAND was significantly improved among the high-dose vamorolone cohort (least-squares mean [LSM], 0.05 [0.01] m/s) compared with the placebo group (LSM, -0.01 [0.01] m/s; 95% CI, 0.02-0.10; P =.002). The significant group differences were observed from week 6 of treatment (P =.02). Significant group differences in TTSTAND were also observed between the low-dose vamorolone and control cohorts (P =.02).
The number of participants reporting any treatment-emergent adverse event was similar between groups, ranging from 79.3% to 89.3%, in which the total count of events was lowest in the placebo group (n=77) and highest in the prednisone group (n=121). One prednisone recipient withdrew from the trial due to adverse events.
Height percentile declined among prednisone recipients (-1.88%), did not change in the low-dose vamorolone cohort (0.26%; P >.05), and increased in the high-dose vamorolone group (3.86%; P =.02). Body mass index (BMI) did not change significantly from baseline in any group.
Biomarkers for bone formation and turnover (osteocalcin, procollagen 1 intact N-terminal propeptide [P1NP], type 1 collagen cross-linked C-telopeptide [CTX1]) decreased from baseline among the prednisone group but not the vamorolone groups (all comparisons, P <.001). The low-dose vamorolone recipients showed less evidence of adrenal suppression than the prednisone group on the basis of morning cortisol levels (P <.001) and high-dose vamorolone showed higher levels of adrenal suppression than prednisone (P =.03).
“The proven efficacy over a broad dose range (2-6mg/kg per day) may enable physicians to adjust dose based on clinical observations and patient preferences,” the researchers concluded.
This study was interrupted by the COVID-19 pandemic and some follow-up data were missing.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Guglieri M, Clemens PR, Perlman SJ, et al. Efficacy and safety of vamorolone vs placebo and prednisone among boys with Duchenne muscular dystrophy: a randomized clinical trial. JAMA Neurol. Published online August 29 2022. doi:10.1001/jamaneurol.2022.2480