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Monitoring and Pharmacodynamic Effect of Eftrenonacog-Alfa (Alprolix®) in Severe Hemophilia B Patients: A Real-Life Study

1Service d'Hématologie Biologique, AP-HP, Centre-Université de Paris, Hôpital Cochin, Paris, France, 2Centre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, AP-HP, Centre-Université de Paris, Hôpital Cochin, Paris, France, 3Université de Paris, Faculté de Santé, Paris, France, 4Laboratoire de Biomathématiques, EA 7537, Faculté de Pharmacie, Université de Paris, Paris, France, 5Service de Biostatistiques et Informatique Médicale SBIM, Hôpital Saint Louis, AP-HP, Paris, France, 6Université de Paris, Innovative Therapies in Haemostasis, INSERM 1140, Paris, France

Abstract Number: PB0320

Meeting: ISTH 2020 Congress

Theme: Coagulation and Natural Anticoagulants » FVIII/IX

Background: Eftrenonacog-alfa is a recombinant factor IX-Fc fusion protein (rFIX-Fc) increasingly prescribed in hemophilia B patients due to its extended half-life. A wide variation in FIX activity measurement has been reported in spiked samples.

Aims: Compare chromogenic (CSA) and one-stage clotting (OSA) assays to product-specific OSA for eftrenonacog-alfa monitoring and assess its pharmacodynamics (PD) in real-life setting.

Methods: Sixty samples from 15 severe hemophilia B treated patients were collected at different time points. FIX activity was measured using CK Prest OSA with a product-specific or a standard calibrator, Biophen FIX and Rox FIX. Thrombin generation assay (TGA) was triggered in 56 samples with 1 pM tissue factor. Five parameters were analyzed: lag time (LT), time to peak (TTP), peak height (PH), endogenous thrombin potential (ETP), and velocity. PD models were built to characterize their relationships with FIX activity level, using mixed effects models.

Results: Standard OSA significantly underestimated FIX (median difference -42% [min -79.5 – max 8.0]) compared to product-specific OSA throughout the measuring range (21.5, [1-86] IU/dL). Biophen FIX and Rox FIX allowed reliable measurements except in samples with FIX < 20 IU/dL (n = 30) in which FIX was underestimated (difference > 30%) in 43 and 37%, respectively. Bias correction using inverse linear regression functions increased the uncertainty of measurement making the corrected values unreliable. Velocity was the most sensitive TGA parameter to FIX level followed by PH, then ETP, TTP and finally LT. Pharmacokinetic models suggested that following the peak of FIX activity obtained after eftrenonacog-alfa injection, TGA velocity decreased first, followed by PH then ETP.

Conclusions: Both CSA and standard OSA failed to accurately measure FIX in severe hemophilia B patients treated with eftrenonacog-alfa throughout the measuring range in comparison to product-specific assay. TGA could be an additional valuable tool to evaluate hemostasis balance in treated patients.

To cite this abstract in AMA style:

Atsou S, Furlan F, Duchemin J, Ellouze S, Sourdeau E, Launois A, Roussel-Robert V, Stieltjes N, Combe S, Fontenay M, Curis E, Jourdi G. Monitoring and Pharmacodynamic Effect of Eftrenonacog-Alfa (Alprolix®) in Severe Hemophilia B Patients: A Real-Life Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/monitoring-and-pharmacodynamic-effect-of-eftrenonacog-alfa-alprolix-in-severe-hemophilia-b-patients-a-real-life-study/. Accessed January 28, 2022.

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