Expansion of prednisone-responsive bone and chondrocyte biomarkers in the vamorolone trials: Further differentiation of vamorolone from prednisone


Clinical Trials

Poster Number: M177


Rebecca Tobin, Carleton University, ON, Canada, Leanne Ward, MD, Children's Hospital of Eastern Ontario, Canada, Paula Clemens, MD, University of Pittsburgh, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, VBP15-004 Investigators, CINRG, Yetrib Hathout, Phd, Binghamton University, Eric Hoffman, PhD, Binghamton University, Binghamton, NY, USA, Utkarsh Dang, PhD, Carleton University

Vamorolone is a steroidal anti-inflammatory, recently approved (FDA) for boys with Duchenne muscular dystrophy (DMD), 2 years and older. In the phase 2b VBP15-004 study, chronic treatment with prednisone was associated with a decrease in growth velocity and suppression of bone turnover markers (osteocalcin (OC) procollagen I N-terminal propeptide [P1NP], collagen I C-Telopeptide [CTX1]).

To use SOMAscan profiling of sera from boys with DMD, age 4-<7 years at baseline from the double-blind placebo- and prednisone controlled trial of vamorolone to expand the repertoire of prednisone-responsive bone and cartilage biomarkers. Methods Longitudinal (baseline, weeks 12, 24, and 48) serum samples were assayed using a SOMAscan 7,000 aptamer panel. A data mask was applied, limiting to 1,500 of these proteins, based on literature and expert opinion. A mixed models for repeated measures approach was used to study acute change, stability of change; to compare prednisone, vamorolone, and placebo; and to study cross-over from prednisone to vamorolone. Multiple testing correction was used. Results Several biomarkers, each associated with bone and cartilage metabolism, were significantly decreased by prednisone treatment but not by vamorolone or placebo: collagen alpha-1(X) chain [COL10A1], collagen alpha-2(XI) chain [COL11A2], chondrocalcin [COL2A1], aggrecan core protein [ACAN], biglycan [BGN]], hyaluronan and proteoglycan link protein 1 [HAPLN1], and osteopetrosis-associated transmembrane protein 1 [OSTM1]. On transitioning from prednisone to vamorolone 6 mg/kg/day, all 7 biomarkers returned to baseline levels. Conclusions Seven biomarkers for bone, growth plate and articular chondrocytes were found to react similarly to osteocalcin, P1NP, and CTX1 with prednisone treatment in DMD. None of these bone turnover biomarkers were reduced by vamorolone, and each returned to normal (placebo) levels upon cross-over from prednisone to vamorolone. These 7 new bone and cartilage associated biomarkers add additional support for improved bone and growth plate metabolism with vamorolone.