Pivotal trial of vamorolone in Duchenne muscular dystrophy

Abstract ReveraGen BioPharma is a clinical stage drug development company that is developing vamoroloneVBPa first in class dissociative steroidal drugThe initial indication being tested is Duchenne muscular dystrophyDMDwhere vamorolone holds promise for retaining or increasing efficacy of glucocorticoidswhile reducing adverse effectsbone fragilitystunting of growthweight gaininsulin resistanceReveraGen received a NINDS SBIR Phase II grant in support of the Phasea studies into andltyear old DMD boys inprotocols VBPVBPRNSThe original trial was planned for four dose groupswithboys per dose groupup topatientsAfter award of the grantthe size of the trial was increased toDMD boysper dose groupnDespite the narrow age range in a rare diseasethe trial was fully enrolled withinmonthsand the Phasea study completed in Novemberwithin the time frame of the SBIR Phase II grantFebruaryJanuaryAll doses were well toleratedmg k gdaymg kg dayor totimes the typical prednisone dose in DMD boysPharmacokinetics showed a wellbehaved drugwith PK similar to corticosteroidsshort half life ofhrsand no drug accumulation between dosesThere was no significant change in body mass indexprimary clinical safety outcome relative to prednisonePharmacodynamic biomarker results showed improved safety compared to corticosteroidswith no evidence of insulin resistance at any doseand a andgtfold improved safety margin for bone turnover and adrenal suppressionHerewe request partial support for the pivotal double blind Phaseb study ofDMD boysagesto andltyearsThe Phaseb studyVBPincludes four groups with six months treatmentplaceboprednisonelow dose vamorolonehigh dose vamorolonefollowed by an additionalmonths treatment with two dose levels of vamoroloneCo funding for the Phaseb study is from the European Commission$ M Horizonsgrant awarded inventure philanthropy support by non profit foundationsand an option agreement for future sales and marketingAimis to testmonths of treatment of two dose levels of vamorolonewith efficacytime to standvsplaceboand safetychange in body mass indexvsprednisoneAimis to bridge pharmacodynamic biomarkers to clinical outcomes of both safety and efficacyAnticipated new matching funding during the proposed award period includes and milestone payment on the option agreement$M AugustThe completion of the proposed Phase IIB SBIR research will lead to discussions with the FDA regarding possible accelerated approvalwith Phase III trials in the post marketing periodThe bridging of novel safety and efficacy biomarkers to clinical outcomes will enable the utilization of these biomarkers to expand labeling to younger DMD childrenyearsand efficient testing of vamorolone for treatment of new indicationsegBecker muscular dystrophyjuvenile dermatomyositisthus providing the potential to significantly augment the treatment options and quality of life for patients with genetic and autoimmune neuromuscular disorders Project Narrative Funds are requested to carry out a clinical trial entitledA Phase IIb RandomizedDouble blindParallel GroupPlaceboand Active controlled Study with Double Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys with Duchenne Muscular DystrophyDMDVBPThis current application is a competitive renewal of a SBIR Phase II supported open label studies of vamorolone inDMDto andltyear boys that were successfully completedVBPVBPIn the proposed Phaseb trialtwo doses of vamorolone will be compared to prednisone treatedand placebo treatedenrollingDMD boyswith multiple outcomes for safety and efficacyExploratory research on mobile health outcomesactigraphand pharmacodynamic biomarkers will be carried out