Four clinical trials of vamorolone in DMD patients have been completed in the project lifetime; A Phase 2a open-label, multiple ascending dose study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and exploratory efficacy was completed in May 2018. (VBP15-002; NCT02760264). This was followed by a Phase 2a extension study to assess long term safety and efficacy (VBP15-003; NCT02760277) and a further long term extension study. (VBP15-LTE NCT03038399). These Phase 2a studies were conducted at eleven Cooperative International Neuromuscular Research Group (CINRG) study sites, in the USA, Canada, Israel, Sweden, the UK and Australia. Subjects were enrolled in four dose cohorts sequentially from 0.25 mg/kg up to 6.0 mg/kg of vamorolone. The primary outcome was the acute safety, tolerability, and pharmacokinetics of vamorolone in DMD boys. The results of the first study have been published (Conklin et al. 2018). At the end of the Phase 2a study, all patients were enrolled into the Phase2a 24-week extension study (VBP15-003), at the same vamorolone dose level they were assigned in VBP15-002. This extension study has also been completed.
The fourth vamorolone clinical trial (Phase 2b -VBP15-004; NCT03439670) was completed in August 2021 across 33 sites in 11 countries including the US, Canada, Belgium, Czech Republic, Greece, Israel, Netherlands, Spain, Sweden, UK, and Australia. The Phase 2b study was a randomized, double-blind, parallel group, placebo and active-controlled study to evaluate the efficacy, safety, PD, and population PK of vamorolone administered orally, at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone 0.75 mg/kg/day, and placebo over a Treatment Period of 24 weeks, and to evaluate persistence of effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to <7 years with DMD.
Topline results indicate vamorolone given throughout the study showed sustained efficacy, across multiple endpoints over 48 weeks. The good safety and tolerability profile was confirmed. The FDA considered the safety and efficacy data of vamorolone at 24 weeks (period 1) was sufficient for a New Drug Application (NDA) filing.
The VISION-DMD project has carried out a series of biomarker discovery and validation studies. This has included research into biomarkers (serum protein and miRNA; DNA genetic modifiers) that influence disease severity and response to steroidal drug treatment (corticosteroids and vamorolone). Work successfully defined six exploratory efficacy biomarkers for drug anti-inflammatory effects and validated these biomarkers in 4 steroid-responsive disease states (three paediatric). This work was published in a peer-reviewed manuscript (Conklin et al. 2018a). Serum samples have been collected and banked in all 4 vamorolone clinical trials.
