PB0193 - Dose optimization for prophylaxis using a pharmacokinetic model for factor IX products in severe hemophilia B

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

BV

Björn Vandewalle

Vice Director, Science & Innovation
Exigo Consultores, Lisbon, Portugal
Lisbon, Lisboa, Portugal
GC

Giancarlo Castaman

Medical Director
Center for Bleeding Disorders and Coagulation, Department of Oncology, Careggi University Hospital, Florence, Italy
Florence, Toscana, Italy
María Teresa Alvarez-Román, MD, PhD

Head of the Thrombosis and Haemostasis Unit
La Paz University Hospital, Madrid, Spain
Madrid, Madrid, Spain
Carmen Escuriola-Ettingshausen, MD

Physician
Haemophilia Centre Rhine-Main, Mörfelden-Walldorf, Germany
Mörfelden-Walldorf, Hessen, Germany
LN

Laszlo Nemes

Director of the National Haemophilia Center and Haemostasis Department
Medical Center of Hungarian Defence Forces
Budapest, Budapest, Hungary
Radovan Tomic, MPharm, MSc

Director Market Access Europe
CSL Behring
Milan, Lombardia, Italy
PM

Paulo Martins

Quantitative Analyst
Exigo Consultores, Lisbon, Portugal
Lisbon, Lisboa, Portugal
JR

Joana F. Rodrigues

Global Medical Affairs Associate Director, Hematology
CSL Behring
Marburg, Hessen, Germany

Presenting Author(s)

Karen Pinachyan, MD

Head of Medical Affairs Europe
CSL Behring Europe
Mechelen, Antwerpen, Belgium

Background: Trough factor IX (FIX) levels have been used as a proxy for bleeding control in patients with hemophilia B. However, there is some debate about the exact correlation between trough levels and bleeding phenotype and which trough levels are optimal for effective, manageable treatment. Understanding the pharmacokinetic (PK) properties under prophylactic utilization of FIX products is imperative for achieving and maintaining desired FIX trough levels, improving patients’ quality of life, and managing treatment resources.

Aims: This population PK model-based analysis aimed to assess optimal dosing and administration frequency to achieve predefined FIX activity trough levels for a range of different FIX replacement products in patients with severe hemophilia B.

Methods: The model used a hypothetical simulated 10,000 patient population and employed published population PK models to compare extended half life factor FIX products available in Europe (rIX‑FP, rFIXFc, N9-GP), considering posologies based on their respective product labels.

Results: The capacity of FIX products in achieving predefined trough levels was effectively estimated by the model, predicting the optimum dosing and administration frequency required (Table 1). This provides a greater understanding of PK and consumption of FIX products, allowing for a more individualized, patient-clinician shared decision making approach, focused on reducing treatment burden, increasing trough levels and improving bleeding control. The model indicates that some FIX products were unable to reach certain trough levels (or for a low proportion of patients only). For those products that did consistently reach target trough levels, a reduced treatment burden and consequent lower FIX consumption was observed. This may also improve resource utilization and treatment costs, whilst maintaining or reducing the bleeding risk.

Conclusion(s): This model-based assessment should help broaden the understanding of different FIX product capabilities and provide optimal dosing strategies, facilitating individualization of care.