Golimumab Biosimilar AVT05 Exhibits Pharmacokinetic Similarity

The proposed golimumab biosimilar, AVT05, demonstrated pharmacokinetic (PK) similarity as well as safety, tolerability, and immunogenicity compared with the reference product among a cohort of healthy participants, according to data presented at the 2024 European Congress of Rheumatology (EULAR).¹

Alvotech’s AVT05 inhibits tumor necrosis factor alpha (TNF-α), which has been shown to impact several chronic inflammatory diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis. Alvotech, the first company to announce positive results from a trial evaluating a golimumab biosimilar, is only 1 of 2 companies to have initiated a patient study in this area. The biosimilar has not been granted regulatory approval in any country and biosimilarity has not been established by regulatory authorities.²

Previous research has evaluated the recombinant human IgG1қ monoclonal antibody (mAb) in a group of patients with moderate to severe RA. The randomized, double-blind, 2-arm, multicenter confirmatory clinical study was designed to determine the safety, efficacy, and immunogenicity between the proposed biosimilar and reference drug for the treatment of RA. The primary endpoint was the change from baseline to week 16 in Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP).²

At the end of the trial, the study met its primary outcome, indicating therapeutic equivalence between the biosimilar and reference product. Further, there were no clinically meaningful differences in safety through week 24.²

In the current study, a team of investigators led by Chris Wynne, MBChB, chief scientific officer at New Zealand Clinical Research (NZCR), recruited 336 healthy adult patients aged 18 to 55 years were randomized 1:1:1 to receive AVT05, the US reference product, or the European reference product. All patients were given a 50 mg/.5 mL subcutaneous injection on day 1 and were followed through day 75. The primary PK endpoints were the maximum serum concentration (C_max) and area under the serum concentration-time curve from time zero to infinity (AUC_0-inf). PK similarity was met if the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for both endpoints is contained within the prespecified margins of 80 – 125% for all 6 pairwise treatment comparisons. Additional endpoints were other PK parameters and safety, tolerability, and immunogenicity.¹

Demographic and baseline characteristics were comparable across treatment arms. The 90% CI for GMR for both primary PK parameters for all 3 pairwise comparisons were within the prespecified margins. Further, the secondary PK parameters and the mean serum golimumab concentrations through day 75 were similar across treatment arms.¹

Most (66.1%) patients reported ≥ 1 treatment-emergent adverse event (TEAE) during the 75-day period, although the frequency was similar across treatment groups. Most TEAEs were categorized as mild to moderate in severity. Of the 2 serious TEAEs reported in the AVT05 and European reference product groups, neither were thought to be related to treatment. Local administration site reactions were considered mild in severity and reported in 6.1% of those in the AVT05 cohort, 10,8% in the European reference product cohort, and 5.5% in the US reference product cohort.¹

In total, 75.7% (n = 87), 82.9% (n = 92), and 80.9% (n = 89) in the biosimilar, European product, and US product, respectively, were anti-drug antibodies (ADAs) positive. Among these, 57.4% (n = 66), 61.3% (n = 68), and 55.5% (n = 61), respectively, were neutralizing antibodies (Nabs) positive ≥ 1 times throughout the study. The primary PK parameters were slightly lower among ADA positive subjects when compared with ADA negative participants.¹

References

1. ^{Wynne C, Lorch U, Krantz E, Katial, Ashdown T, et al. A Pharmacokinetic (PK) Similarity Study Between AVT05 and Reference Product Golimumab. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.}
2. ^{Pine L. Proposed golimumab biosimilar avt05 meets primary endpoints in moderate to severe RA. HCP Live. April 24, 2024. Accessed July 26, 2024. https://www.hcplive.com/view/proposed-golimumab-biosimilar-avt05-meets-primary-endpoints-in-moderate-to-severe-ra.}