(19.09) MB09 (denosumab biosimilar) vs reference denosumab in PMO Primary results

This was a phase III, randomised, double-blind, parallel, confirmatory study conducted for 12 months in 8 countries (NCT05338086). Women with PMO were randomised to receive 60 mg/mL MB09 or RD subcutaneously, every 6 months (two doses), and stratified by baseline bone mineral density (BMD) lumbar spine T‑score (≤ -3.0 or > -3.0), body mass index ( < 25 or ≥25 kg/m²), age (≥55 - < 68 or ≥68 - ≤80 years), and prior bisphosphonate use (yes/no). Only Main Treatment Period (MTP) will be reported here. Participants went into Transition Study Period (6-month period) after MTP. The primary endpoint was to evaluate the efficacy in terms of percentage change from baseline (%CfB) in lumbar spine BMD at end of MTP. Secondary endpoints included assessment of the efficacy parameters PK/PD (up to month 6), safety, and immunogenicity.

Results: A total of 555 subjects received treatment with MB09 (N=278) or RP (N=277). Demographic and baseline characteristics were well balanced between arms. At month 12, %CfB in lumbar spine BMD results were comparable between both treatment arms and met the predefined equivalence margin. Other efficacy assessments also showed similar results between treatment arms, such as: at months 6 and 12 evaluations, %CfB in lumbar spine, hip and femoral neck BMD and CfB in hip and femoral neck BMD, respectively. PK results demonstrated similar exposure of denosumab, and the geometric least squares (LS) means ratio between arms (95%) for the area under the curve 0 to 6 months fell within the predefined acceptance limits (80.00%, 125.00%).  PD marker (serum carboxy terminal cross linking telopeptide of type I collagen [sCTX]) showed similar suppression between treatment arms: LS means ratio (95% CI) for area under the effect curve for absolute sCTX concentration (AUEC) fell within the 80.00%‑ 125.00% limits. Safety profile was comparable between treatment arms, in terms of nature, frequency, and severity of the adverse events. Anti-drug antibodies incidence was very low across the 12-month assessment.

Discussion/Conclusion:

The results of the primary endpoint demonstrated equivalent efficacy of MB09 to RD in PMO. All secondary efficacy endpoints results supported the therapeutic equivalence between both products. PK/PD profile demonstrated similarity between treatment arms. Safety and immunogenicity profiles were similar to the RD.