Totality of Evidence Supporting the Use of ABP 980, a Trastuzumab Biosimilar: Practical Considerations

Abstract

ABP 980 (KANJINTI™, Amgen, Thousand Oaks, CA, USA; Amgen Europe B.V., The Netherlands) is a biosimilar to trastuzumab (Herceptin ® ), a monoclonal antibody that selectively binds human epidermal growth factor receptor-2 (HER2). Here we provide a brief overview of the totality of evidence (including analytical [structural and functional] characterization, nonclinical evaluation, and human pharmacokinetic [PK], pharmacodynamic, and clinical assessment comparing ABP 980 with trastuzumab reference product [RP]) that supported the approval of ABP 980, along with practical considerations on the reconstitution and use of the lyophilized product to ensure safe and effective administration. ABP 980 has been shown to be highly similar to the RP, with similar mechanism of action, binding, and potency. Key PK parameters, geometric means ratio (GMR [90% CI]) of C max and AUC inf, are comparable and within the equivalence margin of 0.80 to 1.25 (ABP 980: 1.04 [0.99–1.08] versus trastuzumab US: 1.06 [1.00–1.12]; ABP 980: 0.99 [0.95–1.03] versus trastuzumab EU: 1.00 [0.95–1.06]). No clinically meaningful differences were found between ABP 980 and RP in a comparative clinical trial in patients with HER2-positive early breast cancer. Pathological complete response—ABP 980: 48% versus RP: 41% (risk difference [RD], 90% CI: 7.3%, 1.2–13.4; relative risk [RR], 90% CI: 1.188, 1.033–1.366). Sensitivity analyses per central pathology review—ABP 980: 48%; RP: 42% (RD: 5.8%, −0.5 to 12.0; RR: 1.142, 0.993–1.312), with RD and RR falling within predefined equivalence margins. Similar to trastuzumab RP, KANJINTI™ is supplied as a sterile, lyophilized cake to be reconstituted with bacteriostatic water for injection (BWFI) for multiple-dose injection or sterile WFI for single use. Stability data support storage of reconstituted solution at 2–8°C (36–46°F), up to 28\xa0days. Reconstituted solution can be diluted in infusion bags containing 0.9% saline and stored for up to 24\xa0h prior to intravenous administration.