Efficacy and Safety of Biosimilar AVT05 Versus Reference Product Golimumab in Combination with Methotrexate in...

Golimumab is a safe and effective treatment for patients with rheumatoid arthritis. Biosimilars to the reference product (RP; Simponi^®) may make treatment more accessible.

The aim of this study was to assess the efficacy of AVT05, a golimumab biosimilar, and RP, each used in combination with methotrexate, in participants with moderate-to-severe rheumatoid arthritis.

This was a 52-week, randomized, double-blind, two-arm, parallel-group, active-controlled study. Participants were randomized 1:1 to receive AVT05 (n = 251) or RP (n = 251), 50 mg subcutaneously once every 4 weeks to Week 12 inclusive. Randomization was stratified by the baseline Disease Activity Score-28 for Rheumatoid Arthritis using C-Reactive Protein (DAS28-CRP) [≤ 5.1 and > 5.1]. The primary endpoint was the change from baseline in DAS28-CRP at Week 16. At Week 16, responder participants (DAS28-CRP decreased by > 0.6 from baseline and disease activity DAS28-CRP ≤ 5.1) initially enrolled in the AVT05 arm continued to receive AVT05 every 4 weeks. Responder participants initially randomized to RP were re-randomized 1:1 to either continue receiving RP or switch to AVT05. Non-responders were discontinued from the study drug. Change from baseline in DAS28-CRP response criteria at weeks 4, 8, 12, 24, 32, 40, 48, and 52 and percentage of subjects achieving American College of Rheumatology 20/50/70 at weeks 4, 8, 12, 16, 24, 32, 40, 48, and 52 were assessed as secondary endpoints. Safety and immunogenicity endpoints were also assessed.

At Week 16, the least squares mean (standard error) change from baseline in DAS28-CRP in AVT05 and RP was - 2.89 (0.058) and - 2.98 (0.058), respectively. The two-sided 95% confidence interval of the least squares mean difference (0.09; standard error 0.082) was entirely contained within the prespecified equivalence margin of - 0.6, 0.6 (- 0.07, 0.25), supporting a demonstration of comparative efficacy. Two sensitivity analyses (one [S1] without exclusion of any data because of intercurrent events, and one [S2] excluding data following intercurrent events or relevant protocol deviations) supported the robustness of the primary endpoint estimates (S1 95% confidence interval - 0.07, 0.25; S2 95% confidence interval - 0.07, 0.25). There were no notable differences in subgroup analyses. Secondary efficacy analyses were consistent with the primary endpoint, including in participants who switched treatments. Overall safety profiles showed no clinically meaningful differences between treatments, including in participants who switched treatments. Immunogenicity profiles were comparable between treatment arms at all timepoints, including in participants who switched treatments.

Analysis of the change in DAS28-CRP from baseline to Week 16 supported the assessment of comparative efficacy between AVT05 and RP golimumab. Secondary efficacy endpoints were consistent with this, including in participants who switched. AVT05 had a safety and immunogenicity profile similar to that observed for RP at all timepoints, including in participants who switched treatments.

The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT05842213) and the EU Clinical Trials Register (EudraCT Number: 2022-001825-63).