Efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of Bmab 1000 vs reference denosumab: 78-wk results from a randomized, double-blind, multicenter, parallel-arm Phase 3 trial (DEVOTE) in women with postmenopausal osteoporosis.

This randomized, double-blind, multicenter Phase 3 trial evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of Bmab 1000 vs reference denosumab in 479 women with postmenopausal osteoporosis. Participants (mean age 66.6 yr; lumbar spine T-score ≤-2.5 to ≥-4.0) were randomized 1:1 to receive 60 mg Bmab 1000 (n = 238) or reference denosumab (n = 241) subcutaneously. The study comprised 2 parts: Part 1 (weeks 0-52) evaluated therapeutic and PD equivalence between Bmab 1000 and reference denosumab using percentage change from baseline (%CfB) in lumbar spine bone mineral density (BMD) at week 52 and area under the effect curve (AUEC) of serum C-terminal telopeptide of Type 1 collagen (sCTX) from baseline to 26 wk following dosing on day 1 and week 26. Part 2 (weeks 52-78) re-randomized those on reference denosumab to either continue or switch to Bmab 1000 (n = 104 each), while those on Bmab 1000 continued treatment (n = 218). Part 2 monitored the safety of Bmab 1000 and reference denosumab after transition from reference denosumab to Bmab 1000 vs continuing reference denosumab. Secondary analyses included additional efficacy, PD, PK, safety, and immunogenicity parameters. At week 52, the confidence intervals (CIs) for the difference in least square means (LSMs) in %CfB in lumbar spine BMD between Bmab 1000 and reference denosumab were contained within the predefined margins (±1.45; LSM diff: 0.610, 95% CI: -0.095, 1.316), indicating therapeutic equivalence. The sCTX AUEC up to 26 wk for Bmab 1000 and reference denosumab were similar (geometric LSM ratio: 104.14; 95% CI: 97.76, 110.95). The secondary results were comparable among all groups up to week 78, including after transitioning to Bmab 1000 from reference denosumab. In conclusion, Bmab 1000 demonstrated equivalent efficacy and PD to reference denosumab, with similar PK, safety, and immunogenicity profiles. There was no effect of transitioning from reference denosumab to Bmab 1000. Clinical trial registration: EudraCT number: 2021-006545-36, CT.gov number: NCT05345691.