FRI0422 HS016, A PROPOSED ADALIMUMAB BIOSIMILAR, SHOWED EQUIVALENT PHARMACOKINETICS AND SIMILAR SAFETY, IMMUNOGENICITY AND TOLERABILITY TO CHINA-LICENSED ADALIMUMAB IN HEALTHY MALE SUBJECTS, ACCORDING TO A 2.3-MONTHS PHASE I STUDY
Authors: Guoying Cao, Jicheng Yu, Jingjing Wang, Xiaoli Yang, Yu Xue, Jufang Wu, Xiaojie Wu, Jing Zhang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> HS016, a biosimilar to China-licensed adalimumab, has an identical amino acid sequence, similar physicochemical and in vitro functional properties to China-licensed adalimumab. <h3>Objectives</h3> The primary objective of this study was to demonstrate PK equivalence between HS016 and China-licensed adalimumab. PK characteristics, safety, tolerability and immunogenicity were investigated as secondary objectives. <h3>Methods</h3> The first-in-human study was a randomized, double-blind, parallel-control, single-dose study conducted in 136 healthy male subjects at 1 site in China. Subjects were randomized to receive a 40 mg subcutaneous injection of either HS016 or China-licensed adalimumab and were followed up for 70 days. Blood samples were taken pre-dose and at multiple intervals to day 70. The primary outcomes were area under the concentration-time curve from time zero to time t (AUC<sub>0-t</sub>) area under the concentration-time curve from time zero to infinity (AUC<sub>0-∞</sub>), and maximum concentration (C<sub>max</sub>). The secondary endpoints were the time taken to reach the maximum concentration(*T<sub>max</sub>), elimination half-life (T<sub>1/2</sub>) etc. Equivalence for the primary outcomes were to be concluded if the 90% confidence intervals (CIs) for the ratio of geometric least squares means (LS Means) of the groups compared were completely contained within the pre-defined equivalence margin of 0.8 to 1.25 using analysis of variance (ANOVA). Safety indicators mainly included physical examination, vital signs, laboratory examination, electrocardiogram, chest X-ray, etc. Immunogenicity evaluation explored kinetics and magnitude of anti-drug antibody (ADA) and its neutralizing ability of Neutralizing ADA. <h3>Results</h3> The 90% confidence intervals of geometric least squares means ratios (GMR) of C<sub>max</sub>, AUC<sub>0-∞</sub>and AUC<sub>0-t</sub> between HS016 and China-licensed adalimumab arms were (0.9855,1.1359),(0.8743,1.0841) and (0.8724, 1.0605). The 90% confidence intervals of all GMRs fell within pre-specified confidence bounds of 80% to 125%. Of the 136 subjects, 128 had adverse events (AEs) with 63 (92.6%) and 65 (95.6%) AEs occurring in the HS016 and China-licensed adalimumab, respectively. Among these AEs, 172 from 50 subjects (73.5%) in HS016 group and 148 from 55 subject (80.9%) in China-licensed adalimumab were treatment emergent adverse event. The proportion of confirmed anti-drug antibody responses in the 2 study arms were, 25.0% (17 cases) and 22.1% (15 cases) at day 14, 50.0% (34 cases) and 42.6% (29 cases) at day 42, for the HS016 and China-licensed adalimumab arms, respectively. Neutralizing antibodies were all negative at day 14 for both groups, except 2 cases (3.7%) and 1 case (1.6%) at day 42, for the HS016 and China-licensed adalimumab arms, respectively. <h3>Conclusion</h3> It is concluded that HS016 have shown a similar PK to china -licensed adalimumab in healthy male subjects, and no meaningful differences in safety of immunogenicity were observed. <h3>Disclosure of Interests</h3> None declared