Non-Clinical Data

Based on the characterization and optimization of vamorolone for transactivation, transrepression and physicochemical membrane properties, ReveraGen then moved on to testing safety and efficacy in animal models.

Toxicity, pharmacokinetics, pharmacodynamics, and ADME studies (absorption, distribution, metabolism and excretion) have been conducted. Results have demonstrated that most short-term (acute) properties of vamorolone were similar to traditional glucocorticoids.

Key to showing optimization of vamorolone compared to traditional glucocorticoids was more long-term studies of the balance of efficacy (improvement of muscle strength) vs. side effects in mouse models of muscular dystrophy and inflammatory diseases. Multiple studies were conducted using the mdx mouse model of Duchenne muscular dystrophy (a mouse lacking dystrophin in muscle, similar to Duchenne muscular dystrophy patients). Studies used mdx mice at both very young and older ages. Vamorolone consistently showed improvements in muscle function that were similar to or superior to prednisone. Treatment of young mdx mice showed a dose-dependent reduction in muscle inflammation, and improved muscle strength. Vamorolone showed loss of side effects seen with prednisone. These included loss of growth stunting, loss of heart fibrosis, and loss of immunosuppressive effects (Heier et al., 2013).

Other types of muscular dystrophy are also being tested in mouse models, including calpain 3 deficiency (LGMD2A), dysferlin deficiency (LGMD2B) and others.