Vamorolone Improves Motor Function in Patients With DMD


Results from a 24-week phase 2a trial and its 2-year extension suggest that patients taking vamorolone experienced motor outcome improvements compared to corticosteroid-naïve individuals.

Edward C. Smith, MD, associate professor of pediatrics, Duke University, and clinical investigator and lead-author

Edward C. Smith, MD

New results from a multicenter, open-label, 24-week trial (VBP15-003; NCT02760277) and its accompanying 24-month long-term extension (VBP15-LTE; NCT03038399) suggest that patients with Duchenne muscular dystrophy (DMD) who were treated with vamorolone (Santhera Pharmaceuticals) experienced motor outcome improvements compared to corticosteroid-naïve individuals.1,2

The phase 2a study ultimately provides Class III evidence to support the benefit of motor function in boys with DMD with a 2- to 6-mg/kg per day dose. Notably, the data also showed that fewer physician-reported adverse events (AEs) occurred with vamorolone treatment compared to reports of treatment with prednisone and deflazacort, nor was vamorolone treatment associated with stunted growth observed with those agents.

“This long-term study showed significant continued clinical improvement of all outcomes measured over an 18-month follow-up period,” said Edward C. Smith, MD, associate professor of pediatrics, Duke University, and clinical investigator and lead author of the publication, in a statement. “Treatment-related efficacy responses with vamorolone were similar to those seen in an external control group with corticosteroid-treated patients. Both 4-stair climb and 10-meter run/walk tests were significantly improved when compared to steroid-naïve natural history control subjects.”

Smith et al. noted that in addition to these results, which cover the initial 24-week trial and the first 12 months of the VBP15-LTE trial, a phase 3 randomized controlled trial is underway to further investigate safety and efficacy.

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Given the variable timing of dose escalations, Smith and colleagues pre-specified that initial analyses of drug-related efficacy and safety would be limited to those participants who had 18 months of treatment with 2.0 mg/kg per day vamorolone or more (dose group C + dose group D; n = 23). In total, 46 participants with DMD completed the 24-week dose-ranging study, and all continued into the 2-year long extension trial.

In the extension study, Smith et al. noted that “participants were permitted dose escalations and de-escalations at the discretion of families and their physicians.” The majority of them (74%; n = 34) opted to be treated with the highest dose permitted (6 mg/kg per day), and the remaining 26% were dosed with 2.0 mg/kg per day. In total, 2 participants had a dose decreased from 6 mg/kg daily to 2 mg/kg daily due to weight gain.

The individuals with DMD treated with vamorolone (n = 23; aged 4 to <7 years at entry) reported positive improvements from baseline values in time to stand velocity (0.039 event/second; 95% CI, 0.010–0.068; P = .012), run/walk 10-meter velocity (0.356 meters/second; 95% CI, 0.220–0.491; P <.001), 4-stair climb velocity (0.07 event/second; 95% CI, 0.034–0.105; P = .001), 6-minute walk test (62.6 meters; 95% CI, 31.14–93.38; P = .001), and North Star Ambulatory Assessment (4.7 points; 95% CI, 2.702–6.662; P <.001) at month 18.

Additionally, the outcomes in vamorolone-treated DMD patients (n = 46) were compared to group-matched participants in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (corticosteroid-naïve, n = 19; corticosteroid-treated, n = 68) over a similar 18-month period.

In comparison, the time-to-stand values were not markedly different between the vamorolone and corticosteroid-naïve patients (least squares [LS] mean, 0.042; 95% CI –0.007 to 0.091; P = .088), though the difference between the 2 groups for run/walk 10-meter velocity (LS mean, 0.286; 95% CI, 0.104–0.469; P = .003) and 4-stair climb velocity (LS mean, 0.059; 95% CI, 0.007–0.111; P =.027) was significant.

As well, the vamorolone-treatment-associated improvements were similar in magnitude to corticosteroid-related improvements, and those in the corticosteroid-treated group showed stunting of growth (−5.63 percentile [−11.43 percentile for deflazacort; −7.04 percentile for prednisone]), whereas vamorolone-treated trial participants did not (LS mean, 15.86 percentile; 95% CI 8.51–23.22; P <.001).

“Importantly, we also found that vamorolone did not show stunting of growth seen with deflazacort and prednisone, and vamorolone also showed fewer physician-reported adverse events such as mood disturbance, excessive hair growth, and Cushingoid appearance,” said Eric Hoffman, PhD, Vice President of Research, ReveraGen BioPharma, and co-author of the study, in a statement.

Previously, vamorolone was granted orphan drug status in the US and in Europe and has received Fast Track and Rare Pediatric Disease designations by the FDA.

1. Smith EC, Conklin LS, Hoffman EP, et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study. PLOS Medicine. 2020;17(9):e1003222. doi: 10.1371/journal.pmed.1003222
2. Santhera Announces Publication of Long-Term Clinical Data with Vamorolone in Patients with Duchenne Muscular Dystrophy. News release. Pratteln, Switzerland. Santhera. Published September 22, 2020. Accessed October 5, 2020.
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