Amgen is developing a biosimilar of the drug, ABP 959, and during last week’s 24th Congress of the European Hematology Association, held from June 13-16 in Amsterdam, the Netherlands, researchers reported on findings from a phase 1 trial of the proposed product.
Eculizumab (Alexion’s Soliris) is used to treat generalized myasthenia gravis, paroxysmal nocturnal hemoglobinuria, and atypical hemolytic uremic syndrome, all rare and ultra-rare diseases. While effective in treating these diseases, the complement inhibitor is among the highest-cost biologics on the market, carrying a list price of approximately $500,000 per patient per year.
Amgen is developing a biosimilar of the drug, ABP 959, and during last week’s 24th Congress of the European Hematology Association, held June 13-16 in Amsterdam, the Netherlands, researchers reported on findings from a phase 1 trial of the proposed product.
The randomized, double-blind, single-dose, 3-arm, parallel-group study was conducted in 219 healthy volunteers. The volunteers were randomized to receive a 300-mg intravenous infusion of either the proposed biosimilar (n = 71), the EU reference (n = 74), or the US reference (n = 74). Serum samples were collected over 56 days.
The primary objectives were to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of the proposed biosimilar versus the EU and US references, assessed by area under the total serum concentration—time curve (AUC) from time 0 extrapolated to infinity (AUCinf) and area between the effect curve (ABEC) of 50% total hemolytic complement activity (CH50).
Secondary PK endpoints included AUC from time 0 to the time of the last observed quantifiable concentration (AUClast) and maximum observed concentration (Cmax)
The geometric mean ratios of the PK and PD parameters after a single infusion were similar among all 3 groups; the 90% confidence intervals of the geometric mean ratios were fully contained within the prespecified bioequivalence margin of 0.80 to 1.25 for all PK (AUCinf, Cmax, AUClast) and PD (ABEC of CH50) evaluations.
There were no treatment-emergent adverse events (AEs) that led to discontinuation, nor were there any deaths. Five volunteers experienced a total of 8 serious AEs. In total, 8.8% of volunteers had binding antidrug antibodies during the study, and no neutralizing antibodies were detected.
According to the authors, these data show the PK and PD equivalence of the proposed biosimilar to eculizumab, and demonstrated similar safety and immunogenicity profiles.
Chow V, Pan J, Chien D, Mytych D, Hanes V. Pharmacokinetic and pharmacodynamic similarity of ABP 959 with eculizumab: results from a randomized, double-blind, single-dose, parallel-group study in healthy subjects. Presented at: the 24th European Hematology Association Congress; June 13-16, 2019; Amsterdam, the Netherlands. Abstract PF347.