FRI0413 EFFICACY, PHARMACOKINETICS, SAFETY AND IMMUNOGENICITY OF THE BIOSIMILAR HS016 IN COMPARISON WITH ADALIMUMAB IN CHINESE PATIENTS WITH ANKYLOSING SPONDYLITIS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PHASE 3 TRIAL
Authors: Jinmei Su, LI Mengtao, Xiaofeng Zeng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> HS016, a proposed biosimilar to adalimumab, has an identical amino acid sequence, similar physicochemical and in vitro functional properties to adalimumab originator. <h3>Objectives</h3> To assess the efficacy, pharmacokinetic (PK) equivalence, safety and immunogenicity of HS016 compared with adalimumab in Chinese patients with ankylosing spondylitis (AS). <h3>Methods</h3> In a multicenter, randomized, double-blind, parallel-controlled phase 3 study, patients with AS fulfilled with the Modified New York Criteria in 1984 in China were randomized 2:1 to receive HS016 or adalimumab with a dose of 40mg every other week for 24 weeks. Blood samples for PK analyses were collected in about half of AS patients pre-dose every other week and during week 12 and week 14. Samples for anti-drug antibodies (ADA) and neutralizing antibodies (NAb) were analyzed in all patients. The primary endpoint was the proportion of patients achieving 20% improvement in Assessment in SpondyloArthritis International Society (ASAS 20) at week 24. Equivalent efficacy was concluded if 90% confidence interval (CI) of the difference in ASAS 20 response rate was between -15% and 15%. The secondary endpoints included the ASAS 20 response rate at week 12, ASAS 40, 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS5/6 response rate at week 12 and week 24, PK, safety and immunogenicity. <h3>Results</h3> 416 patients were randomly assigned to receive HS016 and 232 to receive adalimumab. The ASAS 20 response rates at week 24 were 87.50% and 90.09% in HS016 and adalimumab groups, respectively, and the difference was -2.59% (90%CI, -6.77% to 1.60%), demonstrating clinical equivalence between HS016 and adalimumab. No significant difference of the proportion of ASAS 40, BASDAI 50 and ASAS 5/6 between the two groups were detected at week 12 or week 24 (table 1). Pharmacokinetic values from 188 AS patients in HS016 group and 109 in adalimumab group were analyzed. The geometric means for steady-state maximum plasma concentration (C <sub>max</sub>) and area under the plasma concentration-time curve from time zero to infinity (AUC<sub>inf</sub>) were similar between HS016 group and adalimumab group. The proportions of treatment-emergent adverse events, serious adverse events and injection site reactions were similar between the two groups (table 2). The frequencies of ADA and NAb positive were similar between the two groups at different time points. Through week 24, 79.13% of 412 patients in HS016 and 79.91% of 229 patients in adalimumab group developed ADAs, and 17.48% of 412 in HS016 and 18.78% of 229 in adalimumab group developed NAbs. <h3>Conclusion</h3> The results of efficacy, PK, safety, immunogenicity from the study conducted in Chinese AS patients support a high similarity between HS016 and the adalimumab. <h3>Acknowledgement</h3> In addition to Peking Union Medical College Hospital, another 27 sites from China were also involved in the study. The authors thank the investigators who made the study possible. <h3>Disclosure of Interests</h3> None declared