Background/Purpose: Dr. Reddy’s-abatacept (DRL_AB) is being developed as a biosimilar to the reference product (RP) (RP-US licensed Orencia®) and the reference medicinal product (RMP) (RMP-EU approved Orencia®). The primary objective of this study was to demonstrate PK similarity of DRL_AB compared to RP and RMP as well as between RP and the RMP following a single 750 mg intravenous (i.v.) dose.

Methods: This Phase I study included healthy male subjects assigned to DRL_AB, RP, or RMP in a randomized, double-blind, parallel group design. The primary objective was to demonstrate PK similarity in terms of AUC0-inf, with secondary objectives including other PK parameters (AUC0-t, Cmax, tmax), safety, tolerability and immunogenicity comparison.

Results: A total of 114 male subjects aged 18 and 50 years with a BMI between 19.3 kg/m2 and 29.6 kg/m2 participated in the study. Baseline characteristics were similar between groups. The AUC0-inf for abatacept following treatment with DRL_AB was comparable to RP and RMP. The 90% CI of T/R ratio for AUC0-inf fell within the bioequivalence criteria (80.00%, 125.00%) when DRL_AB compared with RP or RMP. After correcting for the protein content differences, the 90% CI of T/R ratio for AUC0-inf being 105.27% [99.00%, 111.93%]) for DRL_AB compared to RP and 111.29% [105.15%, 117.78%]) for DRL_AB as compared to RMP. The 90% CIs for AUC0-inf were maintained within the bioequivalence criteria after excluding ADA positive subjects. The secondary PK endpoints (AUC0-t, Cmax, tmax) were also comparable between groups. The 90% CI of T/R ratios for AUC0-t and Cmax fell within the bioequivalence criteria (80.00%, 125.00%) when DRL_AB was compared with RP or RMP. The tmax for abatacept was similar for DRL_AB versus RP or RMP and this was confirmed by non-parametric analysis. A total of 84 subjects experienced at least one Treatment-emergent adverse event (TEAE), with a similar proportion across the DRL_AB (68.4%), RP (81.1%), and RMP (71.8%) groups. Most of the TEAEs (222 out of 238) were of mild severity, while 16 were considered moderate. The incidence of moderate TEAEs was 15.8% in DRL_AB, 8.1% in RP, and 7.7% in RMP groups. Adverse events of special interest (AESIs) like hypersensitivity, viral infections, and other infections were similar between groups. Eight AESIs were reported in 8 subjects (7.0%); 2 (5.3%) in DRL_AB, 2 (5.4%) in RP, and 4 (10.3%) in RMP groups. No deaths or serious adverse events (SAEs) were reported, and all TEAEs resolved without sequelae. The incidence of treatment-emergent ADA positivity was 15.8% in the DRL_AB group, 8.1% in the RP group, and 10.3% in the RMP group. Number of subjects reporting ADA CTLA-4 tested positive with the treatments DRL_AB, RP and RMP were 5 (13.2%), 1 (2.7%), 3 (7.7%) on Day 85 respectively and all these were reported first time at Day 85. The number of subjects reporting neutralizing antibody (NAb) positivity with DRL_AB, RP, and RMP were 0, 1 (2.7%), 0 on Day 15, and 2 (5.3%), 2(5.4%), 3 (7.7%) on Day 85, respectively. The incidence of ADA and NAb, as well as ADA titer, were comparable following treatment with DRL_AB, RP, and RMP.

Conclusion: The study demonstrated PK similarity of DRL_AB with RP and RMP in healthy subjects, with comparable safety and immunogenicity profiles.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacokinetic-similarity-of-drl_ab-a-proposed-biosimilar-abatacept-orencia-results-from-a-randomized-single-dose-double-blind-parallel-arm-comparative-pharmacokinetic-study-in-healthy/