Background/Purpose: ABP 710 is being developed as a biosimilar to infliximab. Both ABP 710 and infliximab reference product (RP) inhibit tumor necrosis factor-alpha and have been shown to be structurally and functionally similar in analytical assessments. In a phase 1 clinical pharmacokinetic (PK) study, both were shown to be bioequivalent for PK parameters. The final step in the demonstration of biosimilarity is a comparative phase 3 clinical trial in a representative indication. The objective of this study was to evaluate the similarity of ABP 710 compared to RP with respect to efficacy across time in patients with active RA.

Methods: In this multicenter, randomized, double-blind, active-controlled, multiple-dose study, the efficacy and safety of ABP 710 was compared with the RP in subjects with moderate to severe RA while being maintained on a stable 7.5 to 25 mg/week dose of methotrexate. Subjects were randomized to receive a 3 mg/kg intravenous infusion of either ABP 710 or RP on day 1 (week 0), at weeks 2 and 6, and every 8 weeks thereafter until week 22. At week 22, subjects initially randomized to RP were re-randomized to either continue RP or transition to receive ABP 710 through week 46. Subjects initially randomized to ABP 710 continued receiving the same treatment through week 46. The primary endpoint of the study was response difference (RD) of ≥20% improvement in ACR (ACR20) at week 22; secondary endpoints included RD of ACR20, ≥50% improvement (ACR50), and ≥70% improvement (ACR70) across time (weeks 2, 6, 14, 30, 34, 38, 36, and 50). Efficacy data were analyzed by initial treatment (ABP 710 or RP) prior to re-randomization and by initial/re-randomized treatment (ABP 710/ABP 710, RP/RP, RP/ABP 710) after re-randomization.

Results: Of the 558 randomized subjects, 556 were treated (ABP 710 n=278; RP n=278); 484 subjects completed the study through week 22 and were re-randomized (ABP 710/ABP 710 n=244; RP/RP n=121; RP/ABP 710 n=119), with 435 subjects completing the study. Results of the ACR20, ACR50, and ACR70 response rates across time for the initial or initial/re-randomized treatment groups were similar, with overlapping 95% confidence intervals (CIs) of ACR response rates between the treatment groups at all time points and narrow RD at all time points (see Table for RDs with 90% CI). Efficacy was consistently maintained throughout the study, with no impact of the single transition from RP to ABP 710. Through week 22, the percentage of subjects reporting any serious adverse events was 4.1% (ABP 710=3.2%; RP=5.0%) and the binding/neutralizing antibody positive post-baseline in subjects was 58.9%/19.4% (ABP 710=57.1%/18.0%; RP=60.6%/20.8%).

Conclusion:

As demonstrated by the narrow RD of ACRs across the entire study, the efficacy of ABP 710 is similar to the RP. Safety was also found to be similar between treatment groups. In addition to previously reported primary efficacy endpoints, these secondary efficacy results support clinical similarity between ABP 710 and infliximab RP with respect to safety and efficacy.

Table 20190603

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-results-from-a-phase-3-study-of-biosimilar-candidate-abp-710-in-subjects-with-moderate-to-severe-ra/