Background CHS-0214 is in development as a proposed biosimilar of etanercept for the treatment of rheumatoid arthritis (RA) and other auto-immune diseases.
Objectives Equivalence of CHS-0214 to etanercept was demonstrated at 24 weeks in a global confirmatory, safety and efficacy study in patients with RA. This update provides efficacy results at 48 weeks and safety results over 52 weeks (or over 48 weeks for subjects who continued to the open-label safety extension study).
Methods Patients had moderate/severe RA and an inadequate response to methotrexate (MTX). Patients were randomized to CHS-0214 or etanercept (commercial European-sourced) at 50 mg SC QW for 24 weeks (Part 1). Patients achieving ACR20 at Week 24 with no safety concerns then received CHS-0214 50 mg SC QW open-label for 24 weeks (Part 2). Patients continued their stable dose of MTX throughout the study.
Results At Week 24, the response rates were 91.0% vs. 90.6% for ACR20, 67.6% vs. 63.7% for ACR50, and 38.3% vs. 37.9% for ACR70, in the CHS-0214 group (n=256) vs. etanercept group (n=256), respectively. At Week 48, the response rates were 93.8% vs. 92.7% for ACR20, 75.0% vs. 73.6% for ACR50, and 49.6% vs. 51.4% for ACR70, in patients who received CHS-0214 for 48 weeks (n=224) vs. patients who received etanercept for 24 weeks and then switched to CHS-0214 for 24 weeks (n=220), respectively. Thus, response rates were maintained both in patients who were switched at Week 24 from etanercept to CHS-0214 and in patients who received CHS-0214 for 48 weeks.
Over the 52-week study, adverse events (AE) were reported in 74.4% of patients who received CHS-0214 for 48 weeks and 76.6% who received etanercept for 24 weeks and were switched to CHS-0214 for 24 weeks. The majority of adverse events were mild or moderate in severity. No deaths were reported. Serious AEs were reported in 4.6% and 7.5% of patients, and serious AEs related to study drug per the investigator were reported in 0.9% and 1.9% of patients in the CHS-0214 and etanercept/CHS-0214 groups. Binding anti-drug antibodies (ADA) occurred in 1.3% and 4.7% of patients receiving CHS-0214 and etanercept during Part 1. In Part 2, treatment-emergent binding ADA occurred in 1.4% of patients receiving CHS-0214 and 0.7% of patients who switched from etanercept to CHS-0214.
Conclusions This randomized, double-blind, active-control, global study demonstrated equivalence of CHS-0214 to etanercept based on the primary endpoint (ACR20 at Week 24) and maintenance of the efficacy response through Week 48. CHS-0214 was well tolerated and effective in patients with rheumatoid arthritis with no clinically meaningful differences to etanercept with regard to safety and immunogenicity. Over the 52-week study, no clinically meaningful differences in safety, immunogenicity, or efficacy were observed in patients who were switched from etanercept to CHS-0214 in comparison with those who only received CHS-0214.
Disclosure of Interest J. O'Dell Consultant for: Coherus BioSciences, A. Kivitz: None declared, T. Takeuchi Consultant for: AbbVie, Asahi Kasei Pharma, Astellas, Astra Zeneca, BMS, Celtrion, Chugai, Daiichi-Sankyo, Eisai, Eli-Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer, Sanofi-Aventis, Santen, Taisho Toyama, Takeda, Teijin Pharma, Y. Tanaka Consultant for: Abbvie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, GSK, Janssen, Mitsubishi-Tanabe, MSD, Novartis, Pfizer, Santen, Takeda, UCB, I. Louw: None declared, T. Tiabut Grant/research support from: Coherus BioSciences, S. Nakashima Employee of: Daiichi-Sankyo, J. Hodge Shareholder of: Coherus BioSciences, Employee of: Coherus BioSciences, H. Tang Shareholder of: Coherus BioSciences, Employee of: Coherus BioSciences, B. Finck Shareholder of: Coherus BioSciences, Employee of: Coherus BioSciences