Phase III Study to Confirm Clinical Similarity of MB09, a Denosumab Biosimilar, and Prolia® in Postmenopausal Women with Osteoporosis (SIMBA Study).

Background/

Objectives

To assess the clinical similarity in terms of efficacy, pharmacodynamics (PD), pharmacokinetics (PK), safety, and immunogenicity between MB09 (denosumab biosimilar) and the reference product [RP, (Prolia®)] up to 18 months in women with postmenopausal osteoporosis (PMO).

Methods

Women with PMO received three doses of 60 mg of MB09 or RP subcutaneously, every 6 months [two doses in the main treatment period and one dose in the transition period (TP)]. The primary efficacy endpoint was the percent change from baseline (%CfB) in lumbar spine bone mineral density (BMD). Secondary endpoints included other efficacy parameters and PD, PK, safety, and immunogenicity assessments.

Results

A total of 555 subjects received MB09 (N = 278) or RP (N = 277). At month 12, %CfB in lumbar spine BMD was comparable between groups (MB09 versus Prolia) and met the predefined equivalence margins. Secondary efficacy endpoints-%CfB in lumbar spine BMD at 6 months and %CfB in hip and femoral neck BMD at 6 and 12 months-were similar between groups. PD marker (serum carboxy terminal cross linking telopeptide of type I collagen) was similarly suppressed in both groups, and the inhibition was maintained in the TP. PK results showed similar denosumab systemic exposure for MB09 and the RP. Both study treatments were well tolerated with similar safety profiles throughout the study period. The incidence of anti-denosumab antibodies was very low.

Conclusions

MB09 demonstrated equivalent efficacy to the reference denosumab in women with PMO. All secondary efficacy endpoints, together with PD, PK, safety, and immunogenicity assessments, supported MB09 as a denosumab biosimilar (NCT05338086, EudraCT No. 2021-003609-24).