Background/Purpose:

ABP 501 is being developed as a biosimilar candidate to adalimumab (Humira®), a fully human recombinant monoclonal antibody. Evidence from analytical comparisons indicates that ABP 501 is highly similar to adalimumab. Pharmacokinetic equivalence between ABP 501 and adalimumab has been demonstrated in a phase I study. Here we present results from the Phase 3 study evaluating the efficacy, safety and immunogenicity in subjects with moderate to severe rheumatoid arthritis (RA) for the first adalimumab biosimilar candidate.

Methods:

This was a randomized, double-blind, active-controlled, equivalence study in adult subjects with moderate to severe RA who had an inadequate response to methotrexate. Subjects were randomized 1:1 to receive either ABP 501 (n=264) or adalimumab (n=262) 40 mg subcutaneously every 2 weeks until week 22 followed by safety follow-up to week 26. The primary endpoint was risk ratio (RR) of ACR20 at week 24; clinical equivalence was evaluated by comparing the 90% confidence interval (CI) of RR with an equivalence margin of 0.738–1.355 (1/0.738). Key secondary endpoints included ACR50 and ACR70, safety, and immunogenicity.

Results:

Baseline characteristics were well balanced between groups. At week 24, 74.6% of subjects (194/260) in the ABP 501 group and 72.4% (189/261) in the adalimumab group met the ACR20 response criteria; the RR of ACR20 was 1.039 with the 2-sided 90% CI of 0.954–1.133, which fell within the predefined equivalence margin of 0.738–1.355. At week 24, 49.2% of patients (120/244) in the ABP 501 group and 52.0% (131/252) in the adalimumab group met the ACR50 response criteria, and 26.0% of subjects (64/246) in the ABP 501 group and 22.9% (58/253) in the adalimumab group met the ACR70 response criteria. The incidence of treatment-emergent adverse events (TEAEs) was 50.0% for ABP 501 and 54.6% for adalimumab, and the incidence of any adverse event leading to discontinuation of the investigational product was 1.9% in for ABP 501 and 0.8% for adalimumab. The most frequently reported TEAEs were nasopharyngitis (ABP 501, 6.4%; adalimumab, 7.3%), headache (ABP 501, 4.5%; adalimumab, 4.2%), and arthralgia (ABP 501, 3.0%; adalimumab, 3.4%), cough (ABP 501: 2.7%; adalimumab: 3.1%) and upper respiratory tract infection (ABP 501: 1.5%; adalimumab: 3.8%). The incidence of serious TEAEs was 3.8% for ABP 501 and 5.0% for adalimumab; of note, 0.8% of patients in the ABP 501 group and 1.1% in the adalimumab group experienced serious infections. The incidence of binding antibodies was 38.3% in the ABP 501 group and 38.2% in the adalimumab group; incidence of neutralizing antibodies was 9.1% in the ABP 501 group and 11.1% in the adalimumab group.

Conclusion: Clinical equivalence between ABP 501 and adalimumab was demonstrated. The overall safety and immunogenicity of ABP 501 and adalimumab were similar.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/randomized-double-blind-phase-3-study-of-efficacy-and-safety-of-abp-501-compared-with-adalimumab-in-subjects-with-moderate-to-severe-rheumatoid-arthritis/