Santhera Pharmaceuticals (SIX: SANN) and ReveraGen BioPharma, Inc announce that the first patient has been dosed in a Phase 2 pilot study to assess vamorolone in Becker muscular dystrophy (BMD), funded by the U.S. Food and Drug Administration (FDA).
This Phase 2 pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and exploratory clinical efficacy on motor function outcomes of vamorolone compared to placebo over a treatment period of 24 weeks in 39 males (aged ≥18 and <65 years) with BMD (ClinicalTrials.gov id: NCT05166109). Participants will be randomized 2:1 to vamorolone 500 mg (250 mg for body weight <50 kg) daily or placebo. The clinical trial plans to enroll at sites in Pittsburgh (USA) and Padova (Italy).
The study is funded by a USD 1.2 million grant from the FDA under their “Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01)” grants program. The grant adds to existing grants from the National Institutes of Health (NIH) – National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Foundation to Eradicate Duchenne to carry out a clinical trial of vamorolone in adults with BMD.
“There are currently no approved drugs for BMD in any country, and no drugs in clinical development for this indication in the USA or Europe,” said Eric Hoffman, PhD, President and CEO of ReveraGen BioPharma. “Vamorolone has shown efficacy in the pivotal VISION-DMD study in Duchenne muscular dystrophy (DMD), a more severe but related disease, and, based on these findings and its mechanisms of action, this developmental compound may show a benefit in BMD.”
“The treatment of BMD is lacking standard of care recommendations albeit there is a high unmet medical need, and about one fifth of BMD patients use some chronic steroid dosing which is often not well tolerated,” said Shabir Hasham, MD, Chief Medical Officer and Head Global Medical Affairs of Santhera. “Vamorolone could address some important safety concerns that may lead to poor tolerability or early treatment discontinuation, and thus may potentially represent a novel therapeutic approach to the treatment of BMD as a chronic therapy.”
“Vamorolone has been shown to suppress dystrophin-targeted microRNAs, and thus has the potential to increase dystrophin levels in BMD muscle,” said Paula Clemens, MD, University of Pittsburgh School of Medicine, and the Study Chair of the clinical trial.
BMD, the second most common progressive muscle wasting disease, is similar to DMD, but usually milder. It is caused by the same dystrophin gene (allelic) mutations as DMD but shows residual dystrophin protein in muscle, and variable onset and progression of muscle weakness. Additional rationale supporting potential benefits of vamorolone in BMD is based on studies in mouse models, where vamorolone increased dystrophin levels via suppression of inflammation-associated microRNA pathways. On this basis, vamorolone is anticipated to increase dystrophin levels in BMD patient muscle [1-3].
Vamorolone is a drug candidate with a mode of action that binds to the same receptor as corticosteroids but modifies its downstream activity and as such is considered a dissociative anti-inflammatory drug [4-7]. This mechanism has the potential to ‘dissociate’ efficacy from typical steroid safety concerns and therefore vamorolone could emerge as a promising alternative to existing corticosteroids, the current standard of care in children and adolescents with DMD. In the pivotal VISION-DMD study, vamorolone met the primary endpoint Time to Stand (TTSTAND) velocity versus placebo (p=0.002) at 24 weeks of treatment and showed a good safety and tolerability profile. The most commonly reported adverse events versus placebo from the VISION-DMD study were cushingoid features, vomiting and vitamin D deficiency. Adverse events were generally of mild to moderate severity.
Santhera expects to complete the rolling new drug application (NDA) filing for vamorolone in DMD to the U.S. FDA in Q4-2022. Vamorolone has been granted Orphan Drug status in the US and in Europe for DMD, and has received Fast Track and Rare Pediatric Disease designations by the US FDA and Promising Innovative Medicine (PIM) status from the UK MHRA for DMD. Vamorolone is an investigational medicine and is currently not approved for use by any health authority.
 Hoffman EP (2020). Acta Myol. 2020 Dec 1;39(4):179-186. doi: 10.36185/2532-1900-020
 Kinder TB et al (2020). Arthritis Rheumatol. 2020 Jul;72(7):1170-1183. doi: 10.1002/art.41215
 Fiorillo AA et al (2015). Cell Rep. 2015 Sep 8;12(10):1678-90. doi: 10.1016/j.celrep.2015.07.066
 Mah JK et al (2022). JAMA Netw Open. 2022;5(1):e2144178. doi:10.1001/jamanetworkopen.2021.44178
 Guglieri, et al (2022) JAMA. doi:10.1001/jama.2022.4315
 Heier CR at al (2019). Life Science Alliance DOI: 10.26508
 Liu X, et al (2020). Proc Natl Acad Sci USA 117:24285-24293