Abstract
Vamorolone is a first-in-class dissociative steroidal drug that is being developed for Duchenne muscular
dystrophy as a replacement for corticosteroid standard of care (prednisone, deflazacort) by small business
ReveraGen BioPharma. ReveraGen completed first-in-patient studies with the aid of a NINDS SBIR Direct-to-
Phase II award (48 DMD boys; sequential clinical trials VBP15-002, VBP15-003, VBP15-LTE, Expanded
Access Protocol), and these have been published (Conklin et al. 2018; Hoffman et al. 2019). These studies
showed dose-responsive improvements in all measures of motor skills, and loss of side effects (no stunting of
growth, less Cushingoid and weight gain). Biomarkers have been integrated throughout the vamorolone
program, providing objective readouts of drug efficacy and safety that also showed clear dose-response in
these initial open label studies. A double-blind pivotal trial of 120 DMD boys (VBP15-004) is currently 40%
enrolled and recruiting at 31 sites in 11 countries. This pivotal study is supported in part by a NINDS SBIR
Phase IIB award and European Commission Horizons 2020 award, and includes placebo and prednisone
arms. It is anticipated that the trial will be fully enrolled in late 2019 or early 2020, and last-patient last visit
anticipated in Q3 2020 leading to initiation regulatory drug approval procedures in both US (FDA NDA) and
Europe (EMA MAA). ReveraGen has remained a privately held small business, and this has enabled
innovations in clinical trial design, use of biomarkers, and regulatory protocols. For example, ReveraGen
requested the FDA consider Expanded Access Protocols for patients leaving vamorolone clinical trials, as this
would reduce burden on patient families and clinical sites, while maintaining centralized safety information, and
this was approved, leading to a FDA press release encouraging others to consider a similar approach. For this
Commercialization Readiness Pilot (CRP) application, ReveraGen seeks support to fill key gaps identified
through a formal FDA NDA gap analysis carried out in Q3 2019, and to enable worldwide drug approval thus
maximizing thus enabling worldwide drug approval and maximizing market access. Technical assistance
request is to both develop a global regulatory strategy, and development of a global intellectual property
strategy. Support for late stage research and development activities include filling identified gaps is Design and
Quality Systems Controls, and conducting a GLP juvenile toxicity study supporting labeling and prescription to
the newborn period. Completing the goals of the proposed CRP would lead to worldwide commercialization of
vamorolone, and set the stage for expanding vamorolone use in many other clinical disorders were
corticosteroids are effective but the severe burden of side effects limits use.
