P515 Biosimilar candidate ABP 501: immunogenicity results from 2 phase 3 studies
P. Kaur*1, E. Krishnan1, N. Zhang1, A. Kaliyaperumal2
1Amgen, Inc., Biosimilars Division, Thousand Oaks, California, United States, 2Amgen, Inc., Clinical Immunology & BSM, Thousand Oaks, California, United States
ABP 501 is being developed as a biosimilar candidate to adalimumab, a fully human recombinant monoclonal antibody. Regulatory guidance recommends establishment of totality of evidence based on a stepwise approach for the demonstration of biosimilarity. With appropriate scientific justification, extrapolation of clinical data allows a biosimilar product to be labelled for use in indications for which the reference product is approved but not studied as part of the biosimilar clinical programme. For ABP 501, evidence from analytical and pharmacokinetic comparisons indicates that it is highly similar to adalimumab. Results of 2 phase 3 studies have confirmed clinical similarity between ABP 501 and adalimumab with respect to safety, efficacy, and immunogenicity. A key consideration for extrapolation to the gastrointestinal indications is an understanding of the immunogenic potential of ABP 501. Here we present the immunogenicity results for ABP 501 from 2 phase 3 studies with different patient populations.
The 2 clinical studies were randomised, double blind, and active controlled; one was in patients with moderate-to-severe plaque psoriasis (PsO) without concomitant immunosuppressive therapy, and the other in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to methotrexate. Details of the 2 studies have been previously reported. Immunogenicity was assessed using validated electrochemiluminescent assays; assays were developed for both ABP 501 and adalimumab; each serum sample was tested in both assays. Samples positive for binding antidrug antibodies (ADAs) were tested in a TNFα-binding bioassay for neutralising activity.
In the PsO study with an immunologically sensitive population, the incidence of binding antibodies was 55.2% in the ABP 501 group and 63.6% in the adalimumab group; the incidence of neutralising antibodies was 9.8% in the ABP 501 group and 13.9% in the adalimumab group at week 16. In the RA study, the incidence of binding antibodies was 38.3% in the ABP 501 group and 38.2% in the adalimumab group; the incidence of neutralising antibodies was 9.1% in the ABP 501 group and 11.1% in the adalimumab group. The assay sensitivity for ADA is 0.025 μg/mL in the presence of 25 μg/mL drug. The binding antibody assay results for ABP 501 and adalimumab correlated well, with a regression coefficient > 0.9.
No clinically meaningful differences were observed in the development of binding and neutralising ADAs in the ABP 501 and adalimumab arms in both studies, providing evidence of immunological similarity between ABP 501 and adalimumab and potentially supporting extrapolation to other indications including immune-competent patients.