Golimumab Biosimilar Matches Reference Drug in Year-Long RA Trial

People living with moderate-to-severe rheumatoid arthritis (RA) may soon have access to a more affordable treatment option, as new data confirmed that biosimilar AVT05 performed comparably to the reference product (RP) golimumab (Simponi) across efficacy, safety, and immunogenicity measures over 1 year.

The study, published in BioDrugs, was conducted to establish biosimilarity between AVT05 and RP golimumab in support of regulatory submissions to both the FDA and the European Medicines Agency (EMA). Biologic therapies such as golimumab carry high costs that can limit patient access, and biosimilars represent a potential pathway to broader treatment availability without compromising clinical outcomes.

Who Was in the Trial?

The multicenter, randomized, double-blind, parallel-group, active-controlled trial was conducted across 36 European sites between March 2023 and September 2024. Investigators enrolled 502 adults with active RA, randomizing participants 1:1 to receive either AVT05 (n = 251) or RP golimumab (n = 251), each administered as a 50 mg subcutaneous injection once every 4 weeks in combination with methotrexate.

Participants were adults aged 18 to 75 years with a diagnosis of active RA for at least 4 months prior to screening. Eligibility required a Clinical Disease Activity Index score greater than 10.1 at screening, at least 6 swollen and 6 tender joints, and C-reactive protein (CRP) levels above 1 mg/L. All participants had been taking methotrexate at a stable dose for at least 12 weeks prior to enrollment.

The study population was predominantly female (approximately 80%) and white (approximately 99%), with a mean age of roughly 55 years across both arms. While the groups were well balanced at baseline, the narrow racial and ethnic composition of the sample reflects the European site selection and may limit generalizability to broader patient populations.

At week 16, participants who met responder criteria, defined as a decrease in Disease Activity Score-28 for RA using CRP (DAS28-CRP) of more than 0.6 from baseline and a disease activity DAS28-CRP of 5.1 or lower, continued in the study. Responders originally assigned to the RP arm were re-randomized 1:1 to either continue RP or switch to AVT05, allowing investigators to assess the clinical impact of a real-world-like treatment transition.

The Numbers on Efficacy

The primary endpoint was change from baseline in DAS28-CRP at Week 16. The least squares mean change was −2.89 for the AVT05 group and −2.98 for the RP group, yielding a least squares mean difference of 0.09. The 95% confidence interval (−0.07 to 0.25) fell entirely within the prespecified EMA equivalence margin of −0.6 to 0.6, and the 90% confidence interval (−0.05 to 0.22) fell within the FDA margin of −0.6 to 0.54, supporting a finding of comparable efficacy. Two sensitivity analyses produced identical confidence intervals, reinforcing the robustness of the primary result.

Secondary endpoints, including American College of Rheumatology 20/50/70 response rates and changes in the Simplified Disease Activity Index and Clinical Disease Activity Index, were consistent with the primary finding through week 52. Notably, participants who switched from RP to AVT05 at week 16 maintained stable disease activity scores through the end of the study, with no clinically meaningful differences compared to those who remained on their original treatment.

A Comparable Safety Record

The overall incidence of treatment-emergent adverse events (TEAEs) was comparable between arms through week 16, at 38.2% in the AVT05 group and 41.8% in the RP group. The most commonly reported TEAEs included urinary tract infection and, later in the study, upper respiratory tract infection and nasopharyngitis. 1 participant in the RP group died before Week 16 due to a metastatic neoplasm that was assessed as related to study treatment; no deaths occurred after week 16. No new safety signals emerged in either arm.

Immunogenicity profiles were also comparable. Through week 16, treatment-emergent binding anti-drug antibodies were detected in 54.1% of participants in the AVT05 group and 58.3% in the RP group. Neutralizing antibody rates were similarly parallel. Switching from RP to AVT05 did not appear to alter immunogenicity profiles.

Where the Data Fall Short

The authors noted that the sensitivity of the anti-drug antibody assay resulted in nearly all participants testing positive, which made it difficult to evaluate the impact of immunogenicity on efficacy or pharmacokinetic outcomes. Additionally, the 52-week duration, while sufficient for regulatory purposes, may not capture rare long-term adverse events. Longer follow-up studies will be needed to further characterize AVT05's safety profile over time.

The study was funded by Alvotech Swiss AG, the manufacturer of AVT05, and all authors were employees or former employees of the company at the time the research was conducted.

Reference

Luque M, Zhelyazkova K, Vashishta L, et al. 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). doi:10.1007/s40259-025-00748-8