Background SB5 is a biologic agent developed as a biosimilar of the adalimumab reference product (ADL). Pharmacokinetic equivalence was demonstrated in a phase I study in healthy subjects1. Primary efficacy and safety results from a phase III study in rheumatoid arthritis (RA) patients showed equivalent efficacy and comparable safety and were reported previously2.
Objectives To compare secondary efficacy endpoints up to Week 24 in the phase III study of SB5 vs. ADL in patients with moderate-to-severe RA despite methotrexate (MTX) treatment.
Methods Patients with moderate to severe RA despite MTX treatment were randomly assigned to receive 40 mg of either SB5 or ADL administered subcutaneously every other week for 24 weeks. At Week 24, patients on ADL were randomised again to receive 40 mg of either SB5 or ADL subcutaneously every other week for an additional 28 weeks. Patients on SB5 continued to receive SB5. The primary endpoint was the ACR20 response rate at Week 24. Secondary efficacy endpoints up to Week 24, including ACR20, ACR50, ACR70, disease activity score based on 28 joints (DAS28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), and health assessment questionnaire-disability index (HAQ-DI), were compared for patients receiving SB5 and ADL.
Results 544 patients were randomised and 542 patients were included in the full analysis set (SB5 [N=269] or ADL [N=273]) for assessment of secondary efficacy endpoints. ACR response rates (ACR20/50/70) were comparable between the two treatment groups at every visit up to Week 24. DAS28, SDAI, and CDAI were also comparable up to Week 24. The mean change in DAS28 from baseline to Week 24 was −2.74 for SB5 and −2.68 for ADL; the 95% confidence interval of the difference in the least square means between each treatment group was −0.26 to 0.17, which was within the pre-defined equivalence margin of −0.6 to 0.6. Comparable proportions of patients on SB5 and ADL achieved low disease activity and remission at Week 24, as assessed by DAS28, SDAI, and CDAI. Patient reported outcomes, assessed by HAQ-DI, were also comparable between SB5 and ADL up to Week 24. Other efficacy endpoints (ACR-N, EULAR response) were comparable up to Week 24.
Conclusions Efficacy of SB5 and of ADL was comparable up to Week 24 for all secondary efficacy endpoints, as well as for the primary efficacy endpoint.
Shin D et al. Ann Rheum Dis. 2015; 74 (Suppl2: 459–460), FRI0110
Weinblatt ME et al. Arthritis Rheumatol. 2015; 67 (suppl 10), 8L
Disclosure of Interest J. Kay Grant/research support from: AbbVie, Eli Lilly and Company, Pfizer, Genentech, Roche Laboratories, Consultant for: Alexion Pharmaceuticals, Amgen, AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb Company, Crescendo Bioscience, Eli Lilly and Company, Epirus Biopharmaceuticals, Genentech, Hospira, Janssen Biotech, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Pfizer, Samsung Bioepis, Sandoz, Roche Laboratories, UCB, M. Weinblatt Consultant for: AbbVie, Samsung Bioepis, Amgen, E. Keystone Grant/research support from: Pfizer, Roche, Janssen, Amgen, Consultant for: Pfizer, Roche, Janssen, Amgen, BMS, Merck, Celltrion, Samsung Bioepis, M. C. Genovese Consultant for: Samsung Bioepis, A. Baranauskaite Grant/research support from: AbbVie, Samsung Bioepis, S. Y. Cheong Employee of: Samsung Bioepis, J. Ghil Employee of: Samsung Bioepis