A randomized, double-blind, single-dose, three-arm, parallel group study to determine pharmacokinetic similarity of ABP 959 and eculizumab (Soliris®) in healthy male subjects

Abstract

Objectives: ABP 959 is a proposed biosimilar to eculizumab, a monoclonal antibody targeting the human C5 complement protein. The objective of this randomized, double-blind, three-arm, study was to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity of ABP 959 relative to the eculizumab reference product (RP) in healthy adult male subjects. Methods: Eligible subjects aged 18-45 years were randomized to receive a 300-mg IV infusion of ABP 959, or FDA-licensed eculizumab (eculizumab US), or EU-authorized eculizumab (eculizumab EU). Primary PK endpoint was area under the total serum concentration-time curve from 0 to infinity (AUC0−∞); primary PD endpoint was area between the effect curve (ABEC) of CH50-time data. Results: The geometric mean of PK and PD parameters were similar between ABP 959 versus eculizumab US and eculizumab EU; PK and PD similarity was established based on 90% confidence intervals of the geometric mean ratio being within prespecified equivalence margin of 0.8 and 1.25. The incidence of treatment-emergent adverse events was similar across groups. The incidence of binding anti-drug antibodies was similar across treatments; no subjects developed neutralizing antibodies. Conclusions: This study demonstrated PK and PD similarity of ABP 959 to eculizumab RP; safety and immunogenicity profiles were also similar.