0917: Fifty-two-week Results from a Phase 3, Randomized, Double-blind, Active-controlled Clinical Trial to Compare BAT1806/BIIB800, a Proposed Tocilizumab Biosimilar, with a Tocilizumab Reference Product in Subjects with Moderate to Severe RA with an Inadequate Response to Methotrexate

Xiaomei Leng¹, Piotr Leszczynski², Sławomir Jeka³, Shengyun Liu⁴, Huaxiang Liu⁵, Malgorzata Miakisz⁶, Jieruo Gu⁷, Lali Kilasonia⁸, Mykola Stanislavchuk⁹, Xiaolei Yang¹⁰, Yinbo Zhou¹¹, Qingfeng Dong¹¹, Marian Mitroiu¹², Janet Addison¹³ and Xiaofeng Zeng¹⁴, ¹Peking Union Medical College Hospital, Department of Rheumatology and Clinical Immunology, Beijing, China, ²Poznan University of Medical Sciences, Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan, Poland, ³University Hospital No 2 in Bydgoszcz Collegium Medicum UMK, Clinic and Department of Rheumatology and Connective Tissue Diseases, Bydgoszcz, Poland, ⁴First Affiliated Hospital of Zhengzhou University, Department of Rheumatology and Immunology, Zhengzhou, China, ⁵Qilu Hospital of Shandong University, Department of Rheumatology, Jinan, China, ⁶Twoja Przychodnia Centrum Medyczne, Internal Medicine and Rheumatology, Nowa Sól, Poland, ⁷The Third Affiliated Hospital of Sun Yat-sen University, Department of Rheumatology, Guangzhou, China, ⁸Tbilisi Heart and Vascular Clinic Ltd, Rheumatology, Tbilisi, Georgia, ⁹National Pirogov Memorial Medical University, Internal Medicine, Vinnytsia, Ukraine, ¹⁰Bio-Thera Solutions, Ltd., Research and Development, Guangzhou, China, ¹¹Bio-Thera Solutions Ltd, Research and Development, Guangzhou, China, ¹²Biogen International GmbH, Evidence Generation Biosimilars, Baar, Switzerland, ¹³Biogen Idec Ltd, Maidenhead, United Kingdom, ¹⁴Department of Rheumatology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China

Background/Purpose: BAT1806 (also referred to as BIIB800) is a proposed biosimilar to tocilizumab reference product (TCZ). Results of this Phase 3, randomized, double-blind, active-controlled trial demonstrated that BAT1806 has equivalent efficacy and comparable safety, immunogenicity, and pharmacokinetic (PK) profiles as TCZ up to Week 24 (treatment period 1).¹ Here, the results from Weeks 24 to 48 (treatment period 2 [TP2]) are reported.

Methods: The study was conducted in 55 sites in China and Central Europe. Subjects with a diagnosis of RA according to the ACR/EULAR 2010 revised classification for at least 6 months prior to screening and who met the protocol-specified inclusion/exclusion criteria were randomized in a 2:1:1 ratio to one of three treatment groups: (1) BAT1806 up to Week 48, (2) TCZ up to Week 48, or (3) TCZ up to Week 24 followed by BAT1806 from Week 24 to Week 48, administered intravenously every 4 weeks at a dose of 8 mg/kg. Efficacy in terms of ACR20/50/70 response probabilities and DAS28-ESR and DAS28-CRP, PK, safety, and immunogenicity were assessed up to Week 48.

Results: Of 621 randomized subjects, the numbers of subjects continuing into TP2 were 290 (92.9%), 142 (92.2%), and 145 (93.5%) in groups 1, 2, and 3, respectively. Baseline characteristics were similar across groups at Week 24. At Week 48, ACR20 responders as proportions of evaluable subjects were: 253/280 (90.4%), 121/134 (90.3%), and 122/139 (87.8%) for groups 1, 2, and 3, respectively. ACR20/50/70 responses (Figure 1) and mean change in DAS28-ESR and DAS28-CRP (Figure 2) from baseline were comparable across groups. The proportions of subjects with serious treatment-emergent adverse events (TEAEs) in TP2 were similar between the treatment groups (Table 1). No deaths were reported during TP2. Eight subjects in group 1 reported 9 serious TEAEs, 2 of which (pneumonia and salpingo-oophoritis) were possibly treatment related. Five subjects in group 2 reported 5 serious TEAEs, 1 of which was possibly treatment related (laryngitis). Four subjects in group 3 reported 5 serious TEAEs, 1 of which was possibly treatment related (pneumonia). Anti-drug antibodies were reported at least once in 21.0%, 16.2%, and 18.6% of subjects in treatment groups 1, 2, and 3, respectively; of these subjects, all but 1 in the TCZ group tested positive for neutralizing antibodies (Table 1). Geometric mean (CV%) trough serum concentrations (µg/mL) were comparable for the 3 treatment groups: 13.1 (126.5), 12.7 (157.0), 12.4 (180.7) at Week 28 and 12.3 (82.7), 13.4 (89.2), 13.5 (130.6) at Week 44 for groups 1, 2, and 3, respectively. The study was conducted between 2019–2020 during the COVID-19 pandemic. Post-hoc exploratory analyses indicated that the pandemic had limited impact, which was similar between the treatment groups (data not shown).

Conclusion: Efficacy, safety, immunogenicity, and PK profiles were comparable between BAT1806, TCZ/BAT1806, and TCZ throughout TP2. No safety or clinically relevant immunogenicity issues were observed in subjects switched from TCZ to BAT1806

Reference
1. Leng X, et al. Ann Rheum Dis. 2022;81(suppl. 1):388.





Disclosures: X. Leng, None; P. Leszczynski, Eli Lilly, Pfizer, UCB, AstraZeneca; S. Jeka, None; S. Liu, None; H. Liu, None; M. Miakisz, None; J. Gu, None; L. Kilasonia, Sandoz, Amgen, Takeda; M. Stanislavchuk, Pfizer, Orion, Boehringer-Ingelheim; X. Yang, Bio-thera Solutions Ltd; Y. Zhou, Bio-Thera Solutions Ltd.; Q. Dong, Bio-Thera Solutions Ltd.; M. Mitroiu, Biogen; J. Addison, Biogen; X. Zeng, None.