Comparative clinical efficacy and safety of the proposed biosimilar ABP 710 with infliximab reference product in patients with rheumatoid arthritis

Abstract

Background: ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA).

Methods: In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments.

Results: A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups.

Conclusions: These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity.

Trial registration: ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.

Keywords: ABP 710; Biosimilar; Infliximab; Rheumatoid arthritis.

Conflict of interest statement

Dr. Genovese reports personal fees from Amgen, outside the submitted work.

Juan Sanchez-Burson reports consulting and meetings invitations from Pfizer, Eli Lilly, Sandoz, Sanofi, and Janssen.

Dr. Eva Balazs is a Consultant for Amgen and Celltrion, Inc.

Dr. Neal, Dr. Wojciechowski, and Dr. Hala have no conflict of interest to disclose.

Andrea Everding has consulting contracts with Eli Lilly, Novartis, and Abbvie.

Dr. Fanjiang and Dr. Oh are employees of Amgen.

Dr. Cohen reports grants and personal fees from Amgen, grants and personal fees from Boehringer Ingleheim, and grants and personal fees from Pfizer, outside the submitted work.

Figures

Fig. 1

Patient disposition

Fig. 2

a Percentage of patients achieving ACR20, ACR50, and ACR70 by study week, ± 95% CI. ACR20, ACR50, and ACR70 is the 20, 50, and 70%, respectively, improvement from baseline in American College of Rheumatology core set measurements. b Mean ± 95% CI change from baseline DAS28-CRP by study week. c Percentage of Hybrid ACR improvement from baseline ± 95% CI. Hybrid ACR was calculated when all seven ACR components were non-missing. For post week 22, only re-randomized subjects were included