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P377 Evaluation of the pharmacokinetic profiles of SB5 and reference adalimumab

Shin D.1, Kang J.W.2, Park S.2, Cheong S.Y.1, Hong E.*1

1Samsung Bioepis Co., Ltd, Medical Team, Incheon, South Korea 2Samsung Bioepis Co., Ltd, Quality Evaluation Team, Incheon, South Korea

Background

SB5 has been developed as a biosimilar of the reference adalimumab (ADL) which is a TNF-α inhibitor indicated for the treatment of arthritis, plaque psoriasis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, etc. Analytical studies showed that SB5 was highly similar to ADL in structural properties. Pharmacokinetic (PK) results comapring SB5 and ADL in cynomolgus monkeys, healthy subjects, and patients with rheumatoid arthritis (RA) are reported here.

Methods

The pre-clinical PK profiles were evaluated in cynomolgus monkeys following subcutaneous administrations of 32 mg/kg of SB5 or US-ADL every week for 4 weeks. In healthy subjects, the PK equivalence between SB5 vs. EU-ADL, between SB5 vs. US-ADL, and between EU-ADL vs. US-ADL were assessed in a phase I, 40 mg single dose study. [1] Equivalence was to be concluded if the 90% confidence interval (CI) for the ratio of geometric least squares means (LSMeans) of the primary PK parameters (area under the concentration-time curve [AUC] from time zero to infinity [AUCinf], maximum concentration [Cmax], AUC from time zero to the last quantifiable concentration [AUClast]) were within the standard margins of 0.8 to 1.25. The steady state PK were evaluated in a phase III study in patients with RA where patients received 40 mg of either SB5 or EU-ADL every other week for 24 weeks. [2] Serum concentration was measured through electrochemiluminescence for the pre-clinical study and enzyme-linked immunosorbent assay for the clinical studies.

Results

Cmax, time to reach Cmax (Tmax), and the area under the concentration-time curve from time zero to 168 hour (AUC0–168) were similar in cynomolgus monkeys treated with SB5 or US-ADL. In healthy subjects, the 90% CIs for the primary PK parameters for all pairwise comparisons (SB5 vs. EU-ADL, SB5 vs. US-ADL, EU-ADL vs. US-ADL) were within the margin of 0.8 to 1.25, indicating PK equivalence. In patients with RA, the mean trough concentrations were similar at each time point between SB5 (ranging from 3.850 to 6.761 μg/mL) and EU-ADL (ranging from 3.892 to 6.773 μg/mL). Furthermore, in both phase I and phase III studies, the PK profiles were similar between SB5 and the reference products when analysed by the presence of anti-drug antibody, substantiating the similar PK profile.

Conclusion

In addition to the pre-clinical study in cynomolgus monkeys, similar PK profiles were demonstrated between SB5 and ADL in healthy subjects and in patients with RA. Together with the analytical similarity, a similar PK profile could be expected between SB5 and ADL in indications that were not directly studied in the SB5 program.

References:

[1] D Shin et al. (2015), A Phase I Pharmacokinetic Study Comparing SB5, an Adalimumab Biosimilar, and Adalimumab Reference Product (Humira®) in Healthy Subjects, Ann Rheum Dis, 74(Suppl 2): 459

[2] M Weinblatt et al. (2015), A Phase III, Randomized, Double-Blind Clinical Study Comparing SB5, an Adalimumab Biosimilar, with Adalimumab Reference Product (Humira®) in Patients with Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy (24-week Results), Arthritis Rheumatol, 67(Suppl 10).