FRI0116 Pharmacokinetic Results from a Phase 1, Single-Centre, Double-Blind, Randomised, Single-Dose, Parallel Group Study Comparing 5 MG/KG IV Infusion of BOW015 and Reference Infliximab in Healthy Male Volunteers
Authors: J. Lambert, M. Wyand, C. Lassen, L. Shneyer, E. Thomson, J. Kay
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> BOW015 is an IgG1 monoclonal antibody that binds to TNFα, which is being developed as a biosimilar to reference infliximab (rIFX, Remicade®). Preclinical studies demonstrate statistically significant dose-dependent suppression of synovitis in a murine transgenic arthritis model, with BOW015 and rIFX treatment each producing similar inhibition of joint inflammation. This clinical trial is the first-in-human study of BOW015. <h3>Objectives</h3> To compare the pharmacokinetics (PK), safety and immunogenicity of BOW015 to rIFX in healthy Caucasian male volunteers. <h3>Methods</h3> Eighty-four subjects were randomised to receive BOW015 or rIFX. A single 5 mg/kg IV infusion was administered over 2 hours to 43 subjects in the BOW015 group and 41 subjects in the rIFX group in a hospital-based clinical research unit. Subjects were discharged 2 days after the infusion and returned the next day for follow-up and then at 1, 2, 3, 5, 7, 9, and 12 weeks after the infusion. The treatments were compared using analysis of covariance for the PK parameters C<sub>max</sub>, AUC<sub>(0-t)</sub>, and AUC<sub>(0-inf)</sub>. The criterion for PK bioequivalence was that the 90% confidence intervals (CIs) for the geometric mean ratios were contained within the range 0.80 to 1.25. <h3>Results</h3> Study subjects ranged in age from 18 to 45 years with body weight between 60 to 90 kg and body mass index between 19 and 27 kg/m<sup>2</sup>. Geometric mean C<sub>max</sub> was 142.47 μg/mL following BOW015 infusion and 126.74 μg/mL following rIFX infusion. Geometric mean AUC<sub>(0-t)</sub> was 36,211 h.μg/mL and 34,304 h.μg/mL, and geometric mean AUC<sub>(0-inf)</sub> was 36,775 and 34,801 h.μg/mL following BOW015 and rIFX infusions, respectively. Bioequivalence was demonstrated, with 90% CIs for the treatment mean ratios of 1.07 to 1.18 for C<sub>max</sub>, 0.98 to 1.14 for AUC<sub>(0-t)</sub>, and 0.98 to 1.15 for AUC<sub>(0-inf)</sub>. Apparent terminal phase half-life was similar for BOW015 (307.96 hours) and rIFX (280.22 hours). The range and median of time to peak concentration (t<sub>max</sub>) was also similar for BOW015 (range: 2.00–8.00 hours) and rIFX (range: 2.00–12.02 hours). The median t<sub>max</sub> for BOW015 (3.97 hours) and for rIFX (2.05 hours) was not clinically significant and may have resulted from the 2-hour interval between samples and relatively slow drug elimination. Twenty six subjects (60.5%) in the BOW015 group reported 50 treatment-emergent adverse events (TEAEs) and 27 subjects (65.9%) in the rIFX group reported 54 TEAEs. No TEAE resulted in withdrawal from the study. At Week 12, 2 subjects in the rIFX group developed a positive QuantiFERON®-TB Gold test result, both of which were reported as a TEAE. No significant differences in immunogenicity were observed between the two treatment groups, with anti-drug antibodies [ADA]) developing in 8 subjects (18.6%) in the BOW015 group and in 10 subjects (24.4%) in the rIFX group by Week 12. <h3>Conclusions</h3> PK biosimilarity was demonstrated for BOW015 and rIFX. Both treatments were considered to be well-tolerated, with similar safety profiles and no significant difference in the proportion of subjects developing ADA. Taken in combination with efficacy data, these results establish biosimilarity between BOW015 and rIFX. <h3>Acknowledgements</h3> This research was sponsored by EPIRUS Biopharmaceuticals Inc. <h3>Disclosure of Interest</h3> J. Lambert: None declared, M. Wyand Employee of: Epirus Biopharmaceuticals Inc., C. Lassen Employee of: Epirus Biopharmaceuticals Inc., L. Shneyer Shareholder of: Merck, E. Thomson Consultant for: Epirus Biopharmaceuticals, J. Kay Grant/research support from: AbbVie Inc.; Eli Lilly and Company; Pfizer Inc.; Roche Laboratories, Inc. (paid to the University of Massachusetts Medical School), Consultant for: Amgen, Inc.; AbbVie Inc.; AstraZeneca; Boehringer Ingelheim GmbH; Bristol-Myers Squibb Company; Eli Lilly and Company; Epirus Biopharmaceuticals Inc.; Genentech Inc.; Hospira, Inc.; Janssen Biotech, Inc.; Merck Sharp &amp; Dohme Corp.; Nippon Kayaku Co., Ltd.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Samsung Bioepis; Roche Laboratories, Inc.; UCB, Inc.