Background Therapeutic equivalence of BOW015 and reference infliximab (rIFX, Remicade®) was evaluated in subjects with active rheumatoid arthritis (RA) in a 54-week (wk) Phase 3 comparative effectiveness trial, which met its primary end point by demonstrating comparable ACR20 responses for both BOW015 and rIFX at wk 16.1,2
Objectives To determine whether efficacy of BOW015 is equivalent to that of rIFX in suppressing disease activity and improving physical function, when each is administered in combination with methotrexate (MTX).
Methods In this double-blind (DB), active comparator study, 189 subjects with RA (female, 87.8%; mean age, 44.8 years; mean baseline CRP 26.5 mg/L) receiving stable MTX doses (10-20 mg/wk) were randomized 2:1 to receive either BOW015 or rIFX 3 mg/kg IV at wks 0, 2, 6 and 14. In the open-label (OL) phase, responders to BOW015 or rIFX (n=157) received BOW015 3 mg/kg IV every 8 wks at wks 22, 30, 38 and 46, with follow-up at wk 54. Disease Activity Score 28 based on CRP (DAS28-CRP) and Health Assessment Questionnaire Disability Index (HAQ-DI) were each calculated at every subject assessment. Data from the intent-to-treat (ITT) population were analysed both for the DB phase of the study (n=181), through wk 16, and for the OL phase.
Results Baseline disease activity and disability were similarly high in both treatment arms: mean baseline DAS28-CRP was 6.1 for BOW015 and 6.2 for rIFX; mean baseline HAQ-DI was 1.767 for BOW015 and 1.756 for rIFX. During the DB phase, there were no statistically significant differences between treatment arms at any of the time points for either DAS28-CRP or HAQ-DI. At wk 16, there was clinically significant improvement from baseline in both scores for both groups: mean (±SD) DDAS28-CRP: -2.6 (1.3) for BOW015 and-2.5 (1.3) for rIFX; mean (±SD) DHAQ-DI: -0.945 (0.632) for BOW015 and -0.826 (0.712) for rIFX. Mean DAS28-CRP and HAQ-DI at wk 16 reflected significant reductions in disease activity and disability which were maintained throughout the OL phase of the study (to wk 54), reflecting durability of response in all subjects including those who switched from rIFX to BOW015 (Figure).
Conclusions Disease activity and physical function each was similar for BOW015 and rIFX throughout the DB and OL phases of the study, demonstrating durability of the clinical response to BOW015 through 54 weeks. These findings support the primary result of equivalent efficacy of BOW015 and rIFX, as assessed at wk 16 by the primary endpoint of ACR20. Taken in combination with analytical, pharmacokinetic, and safety data, these results establish biosimilarity between BOW015 and rIFX.
Kay J et al. Ann Rheum Dis 2014; 73(Suppl2):64;
Kay J et al. Arthritis Rheumatol. 2014; 66(12):3538.
Acknowledgements This research was sponsored by EPIRUS Biopharmaceuticals Inc.
Disclosure of Interest J. Kay Grant/research support from: AbbVie Inc.; Eli Lilly and Company; Pfizer Inc.; Roche Laboratories, Inc. (paid to the University of Massachusetts Medical School), Consultant for: Amgen, Inc.; AbbVie Inc.; AstraZeneca; Boehringer Ingelheim GmbH; Bristol-Myers Squibb Company; Eli Lilly and Company; Epirus Biopharmaceuticals Inc.; Genentech Inc.; Hospira, Inc.; Janssen Biotech, Inc.; Merck Sharp & Dohme Corp.; Nippon Kayaku Co., Ltd.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Samsung Bioepis; Roche Laboratories, Inc.; UCB, Inc, A. Chopra Consultant for: Epirus Biopharmaceuticals Inc.; Reliance Life Sciences, C. Lassen Employee of: Epirus Biopharmaceuticals Inc., L. Shneyer Shareholder of: Merck, M. Wyand Employee of: Epirus Biopharmaceuticals Inc.