Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study.

Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia®; Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26. At week 52, the REF-DMAb group was re-randomized 1:1 to a third dose of REF-DMAb or switch to GP2411. The primary efficacy endpoint was percentage change from baseline (%CfB) in LS-BMD at week 52. Secondary efficacy endpoints were %CfB in LS-BMD, FN-BMD, and TH-BMD at weeks 26 and 78 (and week 52 for FN-BMD and TH-BMD). Primary PK and PD endpoints were the area under the serum concentration-time curve extrapolated to infinity and maximum drug serum concentration at week 26, and the area under the effect-time curve of the %CfB in serum CTX at week 26. Secondary PK and PD endpoints included drug serum concentrations and %CfB in serum CTX and P1NP during the study period. Similar efficacy was demonstrated at week 52, with 95% CIs of the difference in %CfB in LS-BMD between treatment groups fully contained within prespecified equivalence margins. Similarity in PK and PD was demonstrated at week 26. Immunogenicity was similar between groups and was not impacted by treatment switch. The rate of new vertebral fractures was comparable. Treatment-emergent adverse events were comparable between groups (63.6% [GP2411/GP2411]; 76.0% [REF-DMAb/REF-DMAb]; 76.6% [REF-DMAb/GP2411]). In conclusion, ROSALIA showed similar efficacy, PK and PD, and comparable safety and immunogenicity of GP2411 to REF-DMAb in postmenopausal osteoporosis.

Jeka S ，Dokoupilová E ，Kivitz A ，Żuchowski P ，Vogg B ，Krivtsova N ，Sekhar S ，Banerjee S ，Schwebig A ，Poetzl J ，Body JJ ，Eastell R ... -  《-》

Pharmacokinetics and pharmacodynamics of the proposed biosimilar denosumab GP2411 and reference denosumab in healthy males.

Vogg B ，Poetzl J ，El Galta R ，Fuhr R ，Schwebig A ，Sekhar S ... -  《-》

The Totality of Evidence for SDZ-deno: A Biosimilar to Reference Denosumab.

Vogg B ，Poetzl J ，Schwebig A ，Sekhar S ，Kivitz A ，Krivtsova N ，Renner O ，Body JJ ，Eastell R ... -  《-》

Efficacy and safety of the biosimilar denosumab candidate (Arylia) compared to the reference product (Prolia®) in postmenopausal osteoporosis: a phase III, randomized, two-armed, double-blind, parallel, active-controlled, and noninferiority clinical trial

Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients. In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs). A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of - 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [- 1.34 to 2.11], 0.04 [- 1.61 to 1.69], and 0.41 [- 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs. The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months. ClinicalTrials.gov, NCT03293108 ; Registration date: 2017-09-19.

Jamshidi A ，Vojdanian M ，Soroush M ，Akbarian M ，Aghaei M ，Hajiabbasi A ，Mirfeizi Z ，Khabbazi A ，Alishiri G ，Haghighi A ，Salimzadeh A ，Karimzadeh H ，Shirani F ，Fard MRH ，Nazarinia M ，Soroosh S ，Anjidani N ，Gharibdoost F ... -  《-》

Denosumab biosimilar in postmenopausal osteoporotic women: A randomized, assessor-blind, active-controlled clinical trial.

Singh I ，Jose V ，Patel R ，Arora S ... -  《-》