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P393 Evaluation of pharmacokinetic profiles of SB2 as a biosimilar of reference infliximab

Shin D., Kang J.W., Park S., Lee Y., Lee S.

Samsung Bioepis Co., Ltd., Incheon, South Korea

Background

Based on the totality of evidence with similar analytical, pharmacokinetic (PK) and clinical results, SB2 was approved by European Medicines Agency as a biosimilar of the reference infliximab (INF) for all indications for which INF has been approved. Here we report the PK profiles of SB2 compared to that of INF in two animal models, healthy subjects and patients with rheumatoid arthritis (RA).

Methods

The pre-clinical PK profiles were evaluated in single and repeated dose studies (1, 3, and 10 mg/kg of SB2, European Union sourced INF [EU-INF] or United States sourced INF [US-INF]) in two animal models (Sprague Dawley [SD] rat and transgenic Tg197 mouse). The clinical Phase I pivotal study for PK was conducted in healthy subjects [1]. The subjects received a single 5 mg/kg intravenous infusion of study drugs (SB2, EU-INF or US-INF) and were observed for 10 weeks. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio geometric least squares means (LSMeans) of the primary PK endpoints (area under the concentration-time curve [AUC] from time zero to infinity [AUCinf], AUC from time zero to the last quantifiable concentration [AUClast] and maximum concentration [Cmax]) were within the standard equivalence margin of 0.8 to 1.25. The steady state PK profile was assessed in a Phase III study in RA patients [2]. In this study, the patients received 3 mg/kg of SB2 or EU-INF at weeks 0, 2, 6 and then every 8 weeks up to 46 weeks. PK analyses were performed up to week 30. Infliximab serum concentration was measured through two different enzyme-linked immunosorbent assays for pre-clinical and clinical studies.

Results

In pre-clinical studies, available PK profiles from animal studies showed no significant differences in Cmax and AUClast between SB2, EU-INF and US-INF. In healthy subjects, the 90% CIs for the primary PK parameters were within the pre-defined equivalence margin of 0.8 to 1.25 between SB2 and reference products (SB2 vs. EU-INF and SB2 vs. US-INF). In RA patients, the mean trough level was comparable between SB2 (ranging from 1.915 to 17.965 to μg/mL) and EU-INF (ranging from 2.224 to 16.954 to μg/mL) from week 2 to week 30. The PK profiles were also comparable between SB2 and INF when analysed by the presence of ADA in both Phase I and Phase III clinical studies.

Conclusion

Similar PK profiles of SB2 and reference products were confirmed in pre-clinical and clinical studies. Altogether, the previously demonstrated analytical similarity and the data presented here indicate that similar PK are expected in all indications approved for SB2.

References:

[1] Shin D et al. (2015), A Randomized, Phase I Pharmacokinetic Study Comparing SB2 and Infliximab Reference Product (Remicade®) in Healthy Subjects.

[2] Choe J-Y et al. (2015), A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy