Background ABP 501 is being developed as a biosimilar candidate to adalimumab (Humira®), a fully human recombinant monoclonal antibody (mAb). ABP 501 has the same amino acid sequence and similar post-translational modifications as adalimumab. It is well known that serum antibodies to adalimumab are associated with lower serum adalimumab concentration.1
Objectives To evaluate the pharmacokinetics (PK) and anti-drug antibody (ADA) relationship of ABP 501 and adalimumab sourced from the US and EU.
Methods This was a single-blind, single-dose, three-arm, parallel-group study. Healthy men and women were randomized to receive 40-mg subcutaneous (SC) injection of ABP 501, adalimumab (US), or adalimumab (EU); PK, safety, and immunogenicity were evaluated. For PK evaluation, serum samples were collected predose; 1, 4, 8, 12, and 24 hours postdose; at each return visit (days 3, 4, 5, 6, 7, 8, 9, 11, 14, 16, 22, 29, 36, 43, 50, and 57); and at the end of study (day 63). Serum concentrations of each mAb were determined using a validated electrochemiluminescent (ECL) assay. Individual concentration-time data for all three molecules were analyzed by noncompartmental PK analysis methods. For ADA analysis, serum samples were collected on days 1 (predose), 16, 29, and 63. A screening immunoassay was used to detect and a confirmatory immunoassay was used to confirm the specificity of binding antibodies. All samples were tested against all three test molecules. The assay sensitivity for ADAs in presence of 25 μg/mL drug was approximately 0.02 μg/mL.
Results Results demonstrating the equivalence of PK, safety, and immunogenicity of ABP 501 compared with adalimumab (US) and adalimumab (EU) have been previously presented.2,3 No preexisting ADAs were detected at baseline. Subjects who developed binding antibodies in each group were as follows: ABP 501, 36 (54%); adalimumab (US), 38 (55%); and adalimumab (EU), 45 (67%). Median time to maximum concentration (tmax) and geometric means of maximum observed serum concentration (Cmax) were similar following the single-dose SC injection of all three molecules independent of ADA status. Overall exposure (area under serum concentration-time curve, AUC) was approximately 20%–30% lower in ADA-positive compared with ADA-negative subjects for all three molecules. Consistent with lower exposure were the shorter elimination half-lives (t1/2) in ADA-positive subjects. On average, t1/2 was 6–7 days in ADA-positive subjects compared with 12–15 days in ADA-negative subjects.
Conclusions Results of this analysis demonstrated that ADA status influences the pharmacokinetics of ABP 501, adalimumab (US), and adalimumab (EU). This is in line with the previously published literature. It is important to continue to monitor this relationship in subsequent pivotal studies when comparing the biosimilar candidate to the reference product to understand if there is an associated change in efficacy.
Bartelds GM, et al. Ann Rheum Dis. 2007;66(7):921-926.
Kaur P, et al. Presented at: European League Against Rheumatism Annual Meeting; June 2014; Paris, France. Abstract FRI0264.
Kaur P, et al. Presented at: American College of Rheumatology Annual Meeting; November 2014; Boston, MA. Abstract 1504.
Acknowledgements Michael Moxness, PhD for clinical immunology work, Amy Rasmussen for study management and Monica Ramchandani, PhD for medical writing.
Disclosure of Interest P. Kaur Shareholder of: Amgen stock, Employee of: Amgen, V. Chow Shareholder of: Amgen stock, Employee of: Amgen, N. Zhang Shareholder of: Amgen stock, Employee of: Amgen, R. Markus Shareholder of: Amgen stock, Employee of: Amgen