Efficacy and Safety of Biosimilar AVT05 Versus Reference Product Golimumab in Combination with Methotrexate in Moderate-to-Severe Rheumatoid Arthritis: 52-Week Results of a Randomized, Parallel-Group, Double-Blind Study

BioDrugs (2026) 40:135–149 https://doi.org/10.1007/s40259-025-00748-8 ORIGINAL RESEARCH ARTICLE Efficacy and Safety of Biosimilar AVT05 Versus Reference Product Golimumab in Combination with Methotrexate in Moderate‑to‑Severe Rheumatoid Arthritis: 52‑Week Results of a Randomized, Parallel‑Group, Double‑Blind Study Monica Luque1 · Kristina Zhelyazkova1 · Laxmikant Vashishta1 · Masna Rai1 · Abid Sattar1 · Katarina Petrovic1 · Richard Bucknall1 · Steffen Leutz1 · Fausto Berti1 Accepted: 7 October 2025 / Published online: 3 November 2025 © The Author(s) 2025 Abstract Background Golimumab is a safe and effective treatment for patients with rheumatoid arthritis. Biosimilars to the reference product (RP; Simponi®) may make treatment more accessible. Objectives 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. Methods 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. Results 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. Conclusions 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. Clinical Trial Registration The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT05842213) and the EU Clinical Trials Register (EudraCT Number: 2022-001825-63). Extended author information available on the last page of the article Vol.:(0123456789) 136 Key Summary Points The data from this study support the demonstration of comparable efficacy between biosimilar AVT05 and reference product golimumab, including in participants who switched from the reference product to AVT05. Safety and immunogenicity profiles were comparable between treatment arms after multiple doses of AVT05 or the reference product, including in participants who switched from the reference product to AVT05. This confirmatory efficacy and safety study contributes to the totality of evidence for AVT05 as a biosimilar to reference product golimumab. 1 Introduction A hallmark of immune-mediated rheumatic diseases (IMRDs) is chronic inflammation, evidenced by elevated levels of tumor necrosis factor alpha (TNF-α) in synovial joint fluid. Reducing TNF-α levels has been shown to alleviate symptoms in conditions driven by autoimmune or hyperimmune responses [1]. With advancements in IMRD treatment, TNF-α inhibitors have become integral. When rheumatoid arthritis (RA) remains refractory to conventional disease-modifying antirheumatic drugs or a combination of conventional diseasemodifying antirheumatic drugs and corticosteroids, biologic anti-TNF agents are introduced into the treatment plan [2, 3]. Golimumab is a fully human, IgG1κ monoclonal antibody that binds with high affinity and specificity to both soluble and transmembrane forms of human TNF, inhibiting TNF-α signaling and modulating the immune response in RA. Among TNF-targeting monoclonal antibodies, golimumab exhibits the highest binding and neutralization activity [4–6]. Its efficacy and safety were established through randomized controlled trials, including GO-FORWARD (patients with RA) [7], GO-RAISE (patients with ankylosing spondylitis) [8], GO-REVEAL (patients with psoriatic arthritis) [9], and GO-AHEAD (patients with non-radiographic axial spondylarthritis) [10]. Subsequent open-label extension studies tracked patients for 5 years, assessing long-term treatment persistence. Among biologic-naïve patients with IMRD, golimumab had a 5-year persistence rate of 70%, while in biologic-experienced patients with RA, the rate was approximately 40% [11–15]. Reference product (RP) golimumab is approved in multiple countries worldwide for the treatment of moderate-tosevere RA, either alone or in combination with methotrexate M. Luque et al. (MTX). In 2009, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved golimumab for adults with moderately to severely active RA (in combination with MTX), active psoriatic arthritis (alone or with MTX), active ankylosing spondylitis, and moderate-to-severe ulcerative colitis [16, 17] While biologic therapies such as golimumab are integral in IMRD management, their high cost can limit patient access [18, 19]. Biosimilars may offer a more affordable alternative while maintaining comparable quality, efficacy, and safety to the reference biologic. These products undergo extensive comparability studies (...truncated)