Background PF-06438179, a proposed biosimilar to infliximab, has an identical primary amino acid sequence and similar physicochemical, in vitro, and in vivo functional properties to infliximab.
Objectives The Phase I study was designed to demonstrate pharmacokinetics (PK) similarity of PF-06438179 to infliximab sourced from the US (infliximab-US) and EU (infliximab-EU), and between infliximab-EU and infliximab-US. Safety was also evaluated.
Methods In this double-blind trial (NCT01844804), 151 healthy volunteers, 18-55 years old were randomized 1:1:1 to one of 3 treatment groups, of which 146 received a single 10 mg/kg IV dose of PF-06438179 (n=49), infliximab-US (n=48), or infliximab-EU (n=49). All subjects provided informed consent. PK was evaluated over a period of 8 weeks and safety and immunogenicity were assessed up to 12 weeks. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the area under curve from time 0 to the last time point (AUCT), from time 0 to infinity (AUC0–∞), and maximum concentration (Cmax) were within the 80.00% – 125.00% bioequivalence (BE) acceptance window.
Results The baseline demographics for the 130 subjects evaluable for PK were similar among treatment groups. The 3 study drugs exhibited a similar PK profile, which is characterized by a rapid increase of serum drug concentration during infusion followed by a multi-phasic decline in drug concentrations (Figure). The 90% CI for the ratios of Cmax, AUCT, and AUC0–∞ were within the BE acceptance window of 80.00–125.00% for the comparisons of PF-06438179 to infliximab-US or infliximab-EU, and infliximab-EU to infliximab-US. Similar number of subjects experienced AEs among all 3 treatment groups. Overall the frequency and type of AEs reported were similar across all three treatment groups, although the number of AEs was highest in the infliximab-US group. The 3 treatments had a comparable ADA profile with a somewhat lower incidence of ADA response in the PF-06438179 group. No infusion related reactions were reported.
Conclusions This study demonstrates PK similarity of PF-06438179 to both infliximab-US and infliximab-EU and of infliximab-EU to infliximab-US. The 3 study drugs were generally safe and well-tolerated in this study.
Disclosure of Interest C. Udata Employee of: Pfizer Inc, S. Hua Employee of: Pfizer Inc, D. Yin Employee of: Pfizer Inc, S. Salts Employee of: Pfizer Inc, X. Meng Employee of: Pfizer Inc, M. Rehman Employee of: Pfizer Inc