Santhera Pharmaceuticals (SIX: SANN) announces that partner ReveraGen Biopharma Inc. and their academic collaborators have published new open-label, long-term clinical data on the safety, tolerability and efficacy of vamorolone in patients with Duchenne muscular dystrophy (DMD). These 18-month treatment data extend previously published 24-week treatment data, and show a reduction of corticosteroid-specific side effects and sustained efficacy with vamorolone including clinical improvement through the 18-month follow-up period.
This publication in the journal PLOS Medicine  provides peer-reviewed and detailed open-label data in patients with DMD treated for 18 months with vamorolone. A multi-center, open-label, 24-week trial (VBP15-003; [2, 3]) with a total 24-month long-term extension (VBP15-LTE; ) was conducted by the Cooperative International Neuromuscular Research Group (CINRG) and evaluated drug-related effects of vamorolone on motor outcomes and corticosteroid-associated safety concerns. This publication covers the 24-week Phase 2a trial (VBP15-003) and the first 12 months of the open-label extension trial (VBP15-LTE) adding up to a total treatment period of 18 months.
“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, Durham (North Carolina, USA), clinical investigator and lead-author of the publication. “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.”
“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,” noted Eric Hoffman, PhD, Vice President of Research at ReveraGen BioPharma, Inc. and co-author of the study.
DMD trial participants (4 to <7 years at entry) treated with 2.0 or 6.0 mg/kg/day vamorolone for the full 18-month period (n=23) showed clinical improvement of all motor outcomes from baseline to month 18 (time to stand velocity, p = 0.012 [95% CI 0.010, 0.068 event/second]; run/walk 10 meters velocity, p < 0.001 [95% CI 0.220, 0.491 meters/second]; climb 4 stairs velocity, p = 0.001 [95% CI 0.034, 0.105 event/second]; 6-minute walk test, p = 0.001 [95% CI 31.14, 93.38 meters]; North Star Ambulatory Assessment, p < 0.001 [95% CI 2.702, 6.662 points]). Outcomes in vamorolone-treated DMD patients (n = 46) were compared to group-matched participants in the CINRG Duchenne Natural History Study (corticosteroid-naïve, n = 19; corticosteroid-treated, n = 68) over a similar 18-month period. Time to stand was not significantly different between vamorolone-treated and corticosteroid-naïve participants (p = 0.088; least squares [LS] mean 0.042 [95% CI –0.007, 0.091]), but vamorolone-treated participants showed significant improvement compared to group-matched corticosteroid-naïve participants for run/walk 10 meters velocity (p = 0.003; LS mean 0.286 [95% CI 0.104, 0.469]) and climb 4 stairs velocity (p = 0.027; LS mean 0.059 [95% CI 0.007, 0.111]). The vamorolone-related improvements were similar in magnitude to corticosteroid-related improvements. Corticosteroid-treated participants showed stunting of growth, whereas vamorolone-treated trial participants did not (p < 0.001; LS mean 15.86 [95% CI 8.51, 23.22]). Physician-reported incidences of adverse events (AEs) for Cushingoid appearance, hirsutism, weight gain, and behavior change were less for vamorolone than published incidences for prednisone and deflazacort.
 Smith E, et al. (2020). Efficacy and safety of vamorolone in Duchenne muscular dystrophy: an
18-month interim analysis of a non-randomized open-label extension study. PLOS Medicine, Link
 Clinicaltrials.gov: An Extension Study to Assess Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD), Link
 Hoffman EP et al. (2019). Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology 93: e1312-e1323.
 Clinicaltrials.gov: Long-term Extension Study to Assess Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD), Link
 Heier CR at al. (2013). VBP15, a novel anti‐inflammatory and membrane‐stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med 5: 1569–1585.
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 Heier CR et al. (2019). Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Science Alliance DOI 10.26508/lsa.201800186.
 Liu X et al. (2020). Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment. Proc Natl Acad Sci USA. Link
 Press release “Santhera Exercises Option to Obtain Worldwide Rights to Vamorolone in Duchenne Muscular Dystrophy and All Other Indications”, September 2, 2020, Link
 Clinicaltrials.gov: A Study to Assess the Efficacy and Safety of Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD), Link
 Press release “Santhera Announces Full Enrollment of ReveraGen’s Pivotal VISION-DMD Study with Vamorolone in Duchenne Muscular Dystrophy”, September 11, 2020, Link