Compared with placebo, treatment with odanacatib consistently reduced fracture risk across a range of subgroups in a phase 3 clinical trial.
Data from a Phase 3 Trial suggests that odanacatib (ODN) significantly reduced fracture risk and led to progressive increases in bone marrow density at the lumbar spine (LS) and total hip (TH) versus placebo. The data, which is gleaned from the Long-term Odanacatib Fracture Trial (LOFT), was presented in a poster presentation at the 2015 American College of Rheumatology Annual Meeting being held this week in San Francisco.
ODN is a selective oral inhibitor of cathepsin K. In earlier Phase 2 research, women receiving combinations of ODN (10-50 mg) for 5 years had gains in spine and hip bone marrow density (BMD) and showed larger reductions in bone resorption than bone formation markers. Discontinuation of ODN had resulted in reversal of treatment effects. Phase 3 data mirrors those findings.
Adverse event data also mirrored that of earlier studies. Major cardiovascular events overall were generally balanced but there were numerically more adjudicated strokes in the ODN group. Final blinded, independent adjudication of all major cardiovascular events is ongoing.
In the large cohort, more than 16,000 women across several countries at or over the age of 65 without a baseline radiographic vertebral fracture (VFx) and a TH or femoral neck (FN) BMD T-score between -2.5 and -4.0 or with a prior VFx and a TH or FN T-score between -1.5 and -4.0 were randomized (1:1) to ODN 50 mg/week or placebo. All patients received vitamin D3 (5600 IU/week) and calcium as required to achieve ~1200 mg/day.
Treatment effects on primary endpoints (new and worsening morphometric vertebral, incident hip, non-VFx) were investigated in patient subgroups, including baseline age, race, bisphosphonate intolerance, prior radiographic VFx, and baseline BMD.
Baseline mean age was 72.8 years, 57% were Caucasian, and 46.5% had prior vertebral fracture. The risk reduction of ODN versus placebo for primary fracture endpoints was generally consistent across all subgroups. For morphometric VFx, the relative risk reductions (RRR) for participants with or without prior VFx were 51% and 60%, respectively; for age groups <70 and ≥70 years, the RRRs were 57% and 53%, respectively.