Odanacatib (ODN), a selective oral inhibitor of cathepsin K, is in development for the treatment of osteoporosis. In the primary efficacy analysis of the Phase 3, Long-Term ODN Fracture Trial (LOFT; NCT00529373), ODN significantly reduced fracture risk compared with placebo in postmenopausal women with osteoporosis. Pre-specified subgroup analyses evaluated the efficacy of ODN in patient subgroups.
Women aged ≥65 years, without baseline radiographic vertebral fracture (VFx) and total hip (TH) or femoral neck (FN) BMD T-score between −2.5 and −4.0, or with prior VFx and TH or FN T-score between −1.5 and −4.0, were randomised (1:1) to ODN 50 mg/week or placebo. All received vitamin D3 (5600 IU/week), and calcium as required. Treatment effects on primary endpoints (new and worsening morphometric vertebral, hip, and non-VFx) were investigated in subgroups (including by age, bisphosphonate intolerance, prior radiographic VFx, baseline BMD).
Of 16,713 randomised women (387 centres in 40 countries), 16,071 were analysed. Baseline mean age was 72.8 years, 57% Caucasian, 46% prior VFx. Mean BMD T-scores were: lumbar spine (LS) -2.7, TH -2.4, FN -2.7. The risk reduction of ODN versus placebo for primary fracture endpoints was generally consistent across all subgroups. For morphometric VFx, relative risk reductions (RRR) for participants with or without prior VFx were 51 and 60%, respectively; for age groups <70 and ≥70 years, RRRs were 57 and 53%, respectively; and, by baseline LS BMD T-score tertiles (≥−2.22; −3.25 to <−2.22; ≤−3.25), RRRs were 58, 47 and 54%, respectively. In bisphosphonate-intolerant patients, the RRR for morphometric VFx, hip and non-VFx were 52, 42 and 17%, respectively, consistent with the overall population. Post-hoc statistics revealed no significant interactions.
In postmenopausal women with osteoporosis, the effect of ODN vs placebo was generally consistent among predefined subgroups in reducing the risk of new and worsening morphometric vertebral, hip and non-VFx.
14 May 2016 - 17 May 2016