Abstract
BackgroundThis double-blind, randomized, 78-week study evaluated the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a candidate adalimumab biosimilar, versus adalimumab reference product (Humira®) sourced from the EU (adalimumab-EU) in biologic-naïve patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) (10–25 mg/week). We report results for the first 26 weeks of treatment.MethodsPatients with active RA (N = 597) were randomly assigned (1:1) to PF-06410293 or adalimumab-EU, while continuing with MTX treatment. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 12. Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the ACR20 difference between the two arms was entirely contained within the symmetric equivalence margin (±14%). Additionally, a two-sided 90% CI was calculated by using an asymmetric equivalence margin (−12%, 15%). Secondary efficacy endpoints to week 26 included ACR20/50/70, change from baseline Disease Activity Score based on high-sensitivity C-reactive protein [DAS28–4(CRP)], European League Against Rheumatism (EULAR) response, DAS28–4(CRP) of less than 2.6, and ACR/EULAR remission. QuantiFERON-TB testing was performed at screening and week 26.ResultsPatients (78.7% of whom were female and whose mean age was 52.5 years) had a mean baseline RA duration of 6.8 years. The mean baseline DAS28–4(CRP) values were 5.9 (PF-06410293) and 6.1 (adalimumab-EU). The observed week-12 ACR20 values were 68.7% (PF-06410293) and 72.7% (adalimumab-EU) in the intention-to-treat population. With non-responder imputation, the treatment difference in week-12 ACR20 was −2.98% and corresponding CIs—95% CI (−10.38%, 4.44%) and 90% CI (−9.25%, 3.28%)—were entirely contained within the equivalence margins (symmetric and asymmetric, respectively). The secondary efficacy endpoints were similar between arms. Over 26 weeks, injection-site reactions occurred in 1.7% versus 2.0%, hypersensitivity events in 4.4% versus 8.4%, pneumonia in 0.7% versus 2.0%, and opportunistic infections in 2.4% versus 1.7% in the PF-06410293 and adalimumab-EU arms, respectively. One death due to myocardial infarction occurred (adalimumab-EU arm). Rates of anti-drug antibody incidence were 44.4% (PF-06410293) and 50.5% (adalimumab-EU).ConclusionsThe study results demonstrate that efficacy, safety, and immunogenicity of PF-06410293 and adalimumab-EU were similar during the first 26 weeks of treatment in patients with active RA on background MTX.Trial registrationClinicalTrials.gov Identifier: NCT02480153. First posted on June 24, 2015; EU Clinical Trials Register EudraCT number: 2014-000352-29. Start date: October 27, 2014.
Highlights
This double-blind, randomized, 78-week study evaluated the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a candidate adalimumab biosimilar, versus adalimumab reference product (Humira®) sourced from the EU in biologic-naïve patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) (10–25 mg/week)
The study results demonstrate that efficacy, safety, and immunogenicity of PF-06410293 and adalimumab-EU were similar during the first 26 weeks of treatment in patients with active RA on background MTX
Statistical methods With the assumption of a week-12 American College of Rheumatology 20% improvement (ACR20) response rate of 60% for both PF-06410293 and adalimumab-EU, a sample size of 560 patients was determined to provide about 85% power to demonstrate therapeutic equivalence between the treatment arms, and the symmetric margin of ±14% was used for the primary endpoint
Summary
This double-blind, randomized, 78-week study evaluated the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a candidate adalimumab biosimilar, versus adalimumab reference product (Humira®) sourced from the EU (adalimumab-EU) in biologic-naïve patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) (10–25 mg/week). The introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) has been a major advance in the treatment of patients with rheumatoid arthritis (RA), providing an important addition to the previously available therapy options [1]. The US Food and Drug Administration (FDA) defines a biosimilar as “a biopharmaceutical that is highly similar to an already licensed biologic product (the reference product), notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences in purity, potency, and safety between the two products” [7]. Biosimilars may expand patient access to bDMARDs because of potentially lower drug prices as a result of price competition within the product market, resulting in savings for health-care systems and patients [9,10,11]
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