Pharmacokinetic Similarity of Biosimiliar AVT05 Versus Reference Product Golimumab in Healthy Adults: A Double-Blind,...

AVT05, a recombinant, human, immunoglobulin G1қ monoclonal antibody, is a biosimilar to Simponi^®.

The purpose of this study was to investigate the pharmacokinetic (PK) similarity, safety, tolerability, and immunogenicity between AVT05 and US-licensed and European Union (EU)-approved reference product (RP) golimumab (US-RP and EU-RP, respectively) in healthy adult participants.

Three hundred and thirty-six healthy male and female participants aged 18-55 years were randomized in a 1:1:1 ratio to AVT05, US-RP, or EU-RP. Participants received a single 50 mg/0.5 mL subcutaneous injection on Day 1 and were followed until Day 75. The primary PK endpoints were maximum serum concentration (C_max) and area under the serum concentration-time curve from time zero to infinity (AUC_0-inf). Pharmacokinetic similarity was demonstrated if the 90% confidence intervals for the geometric mean ratio for both AUC_0-inf and C_max were entirely contained within the prespecified margins of 80.00% and 125.00% for all six pairwise treatment comparisons. Secondary endpoints were additional PK parameters (area under the concentration-time curve from time zero to the last quantifiable concentration, time to C_max, terminal elimination rate constant, terminal elimination half-life, apparent volume of distribution, and apparent clearance), safety, tolerability, and immunogenicity.

Demographic and baseline characteristics were balanced between the treatment groups. The 90% confidence intervals for the geometric means ratio for the protein-adjusted primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (C_max [AVT05/US-RP 89.45, 106.75; AVT05/EU-RP 92.33, 110.15; EU-RP/US-RP 88.64, 105.92]; AUC_0-inf [AVT05/US-RP 94.35, 108.40; AVT05/EU-RP 98.46, 113.13; EU-RP/US-RP 89.36, 102.76]), supporting the demonstration of PK similarity. The secondary PK parameters were also comparable between the treatment arms. The mean serum golimumab concentrations through Day 75 post-dose were similar between treatment arms. Overall, 66.1% of participants experienced at least one treatment-emergent adverse event (TEAE) during the study period. The frequency of TEAEs was comparable across the treatment arms. The majority of TEAEs were mild to moderate in severity. There were two serious TEAEs reported (one [0.9%] each in AVT05 and EU-RP arms), neither of which was considered treatment related. Local administration site reactions were mild in severity and observed in 6.1%, 10.8%, and 5.5% of participants in the AVT05, EU-RP, and US-RP arms, respectively. Overall, 87 (75.7%), 92 (82.9%), and 89 (80.9%) participants in the AVT05, EU-RP, and US-RP arms, respectively, were anti-drug antibody positive; among those 66 (57.4%), 68 (61.3%), and 61 (55.5%) participants, respectively, were neutralizing antibody positive at least once during the study. The primary PK parameters (AUC_0-inf and C_max) were slightly lower in antidrug antibody-positive participants compared with antidrug antibody-negative participants.

Following single-dose administration, the study supported a demonstration of PK similarity between AVT05 and EU-RP and US-RP in healthy participants. Safety, tolerability, and immunogenicity profiles were comparable between the treatment arms.

The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05632211).