Abstract
BackgroundABP 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).MethodsIn 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.ResultsA 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.ConclusionsThese 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 registrationClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.
Highlights
ABP 710 is being developed as a biosimilar to infliximab reference product (RP)
The most common reason for discontinuing the study prior to week 22 was due to Adverse event (AE) (11 [3.9%] patients in the ABP 710 treatment group and 14 [5.0%] patients in the infliximab RP treatment group)
Of the 484 patients who were rerandomized at week 22, 244 were initially randomized to ABP 710 and, continued to receive ABP 710 (ABP 710/ABP 710 treatment group); 121 were initially randomized to infliximab RP and were re-randomized to continue receiving infliximab RP (RP/RP treatment group); and 119 initially randomized to infliximab RP were re-randomized to receive ABP 710 (RP/ABP 710 treatment group)
Summary
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. In an effort to provide alternative treatment options, regulatory agencies have established guidelines to provide an abbreviated development and approval pathway for biosimilars. The evaluation of biosimilarity begins with demonstration of analytical (structural, functional, and physiochemical) similarity, which forms the foundation of biosimilarity This is followed by comparative preclinical and clinical pharmacology evaluations, including human pharmacokinetics (PK) and pharmacodynamics, if relevant, and at least one comparative clinical study to evaluate the similarity of efficacy, safety, and immunogenicity in a representative indication using a sensitive patient population and endpoints to complete the totality of evidence
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