Search

Introduction YLB113 is a biosimilar of the reference product (RP), etanercept, under development for treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications. A phase 3 study was conducted in Europe, Japan, and India to compare the efficacy, safety, and immunogenicity of YLB113 with the RP over a treatment period of 52 weeks. Methods Overall, 528 patients with moderate-to-severe RA receiving concomitant methotrexate were randomized to receive a once-weekly, subcutaneous dose of 50 mg YLB113 or the RP. The primary endpoint was ACR20 response rate at week 24, with similarity confirmed if the 95% confidence interval (CI) for YLB113 and the RP was within the range of − 15 to 15%. Safety and immunogenicity endpoints were assessed to week 52. Results Based on the European analysis, in the full analysis set, ACR20 response at week 24 was 83.3% and 88.5% for YLB113 and the RP, respectively. Responses were within the predefined clinical equivalence margin. The sensitivity analysis in the per protocol set revealed a similar proportion of subjects exhibiting ACR20 response at week 24 between groups, with a difference of − 5.1% (95% CI − 11.07 to 0.81). The incidence of treatment-emergent adverse events was comparable between groups, and the incidence of antidrug antibody development to week 24 favored YLB113 (0.8 vs. 8.3%). Conclusions This study demonstrated biosimilarity of YLB113 to the RP regarding efficacy, safety, and immunogenicity in patients with moderate-to-severe RA. Based on the same mechanism of action, biosimilarity could be extrapolated to other therapeutic indications approved for etanercept. Trial registration EudraCT Number: 2015-002,809-12. Electronic Supplementary Material The online version of this article (10.1007/s40744-019-00186-3) contains supplementary material, which is available to authorized users.

Background YLB113 is an investigational biosimilar of the reference product etanercept (ETN), being developed for the treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications of the reference product ETN. Objectives The phase 3 study of YLB113 was conducted in Europe, Japan, and India across more than 100 rheumatology clinics to compare efficacy, safety, and immunogenicity of YLB113 with ETN in patients with RA. Methods A total of 528 patients with moderate-to-severe RA receiving concomitant treatment with methotrexate were randomized to receive a once-weekly dose of 50 mg of subcutaneously administered YLB113 or ETN. The primary end point was the ACR20 response rate at Week 24, with equivalence confirmed if the 95% confidence interval (CI) was within the range of –15% to 15%. Other efficacy end points, such as DAS28 with safety and immunogenicity end points, were assessed periodically up to Week 52. Results The ACR20 response rate at Week 24 was 81.2% for YLB113 and 86.8% for ETN in the full analysis set, with a treatment difference of –5.6% (95% CI: –11.6, 0.5), which was completely within the predefined equivalence margin of −15% to 15%. The result for sensitivity analysis using the per protocol set population revealed that the proportion of subjects who showed ACR20 response at Week 24 was similar between both treatment groups, at –4.6% (95% CI: –10.1, 0.8). The incidence of treatment-emergent adverse events was comparable between YLB113 and ETN (55.5% vs 65.7%), and the incidence of antidrug antibody development up to Week 24 was in favor of YLB113 (0.8% vs 8.3%). Conclusion The present comparative study demonstrated the biosimilarity of YLB113 to ETN on the triad of efficacy, safety, and immunogenicity in patients with moderate-to-severe RA, and thus can be extrapolated to other therapeutic indications approved for ETN. The therapeutic equivalence of YLB113 and ETN in terms of the primary efficacy end point at Week 24 and long-term safety comparability until Week 52 was established with lower immunogenicity. Disclosure of Interests Hisashi Yamanaka Grant/research support from: AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, Speakers bureau: Bristol-Meyers, Astellas, Pfizer, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, YLbio, Naoyuki Kamatani Speakers bureau: I was a speaker in meetings and paid for the speech by YLB Pharma, Teijin Pharma, Chugai, Pfizer, Fuji Yakuhin, Sanwa Kagaku, Asahi Kasei Pharma and Asteras-Amzen BioPharma., Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Toshihiko Hibino Consultant for: I had worked in Japanese Pharmaceutical Company (Showa Yakkako Company Co. Ltd.) as unaffiliated director until 2015 but have no conflict on business including newly built company (Ayumi Pharmaceutical Company Co. Ltd.) since then., Edit Drescher: None declared, Juan Sanchez-Burson: None declared, Manfred Rettenbacher Employee of: I’m an employee of Lupin Pharmaceuticals Ltd., Girish Bhatia: None declared, Snehal Gadve Consultant for: Was working as a consultant for YLB company, Chirag Shah Employee of: I’m an employee of Lupin Pharmaceuticals Ltd., Dhananjay Bakhle Employee of: I’m an employee of Lupin Pharmaceuticals Ltd.