Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria.

Autor: Kulasekararaj A; King's College Hospital NHS Foundation Trust, National Institute of Health Research/Wellcome King's Clinical Research Facility and King's College London, London, UK., Lanza F; Hematology Unit, Hospital of Ravenna, University of Bologna, Bologna, Italy., Arvanitakis A; Department of Translational Medicine, Lund University, Malmö, Sweden.; Department of Haematology, Oncology and Radiation Physics, Skane University Hospital, Malmo, Sweden., Langemeijer S; Department of Hematology, Radboud Universitair Medisch Centrum, Nijmegen, The Netherlands., Chonat S; Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA., Tombak A; Internal Medicine - Hematology Department, Mersin University, Mersin, Turkey., Hanes V; Amgen Inc, Thousand Oaks, California, USA., Cao J; Amgen Inc, Thousand Oaks, California, USA., Miller MJ; Amgen Inc, Thousand Oaks, California, USA., Colbert A; Amgen Inc, Thousand Oaks, California, USA., Shander B; Amgen Inc, Thousand Oaks, California, USA., Mytych DT; Amgen Inc, Thousand Oaks, California, USA., Chow V; Amgen Inc, Thousand Oaks, California, USA., Henary H; Amgen Inc, Thousand Oaks, California, USA.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2024 Nov; Vol. 99 (11), pp. 2108-2117. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1002/ajh.27456
Abstrakt: ABP 959 is a biosimilar to the eculizumab reference product (RP), which is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). This multicenter, randomized, double-blind, active-controlled, two-period crossover study randomized eculizumab RP-treated patients with PNH to one of two treatment sequences (ABP 959/eculizumab RP or eculizumab RP/ABP 959) to evaluate the clinical similarity of ABP 959 when compared with eculizumab RP. This study evaluated the efficacy of ABP 959 when compared with eculizumab RP based on control of intravascular hemolysis as measured by lactate dehydrogenase (LDH) and by the time-adjusted area under the effect curve of LDH. Secondary outcomes included safety, pharmacokinetics, and immunogenicity. Forty-two patients were randomized (20 in the ABP 959/eculizumab RP group and 22 in the eculizumab RP/ABP 959 group) across 25 centers. Similarity of efficacy was established by a ratio of geometric least squares means of LDH (ABP 959/eculizumab RP) of 1.0628, with a one-sided 97.5% upper CI of 1.1576 at week 27, and a geometric means ratio of time-adjusted area under the effect curve (ABP 959 vs. eculizumab RP) of LDH of 0.981, with a 90% CI of 0.9403-1.0239 from week 13 to 27, week 39 to 53, and week 65 to 79. All secondary efficacy endpoints were comparable between treatment groups. No new safety concerns were identified. The results of this study in patients with PNH, along with previously demonstrated similarity of analytical, nonclinical, and clinical pharmacokinetics and pharmacodynamics in healthy volunteers support a demonstration of no clinically meaningful differences between ABP 959 and eculizumab RP. Clinical Trial Registration: NCT03818607.
(© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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