OC 63.3 - Safety and Efficacy of Recombinant Factor IX Fusion Protein (rIX-FP) in Previously Untreated Patients with Hemophilia B

Tuesday, July 12, 2022

3:15 PM – 3:30 PM

Location: ExCel Center, ICC Capital Suite Room 7&12

Presentation Format: In-Person

Presenting Author(s)

Richard Lemons, MD PhD

Medical Director, Division of Pediatric Hematology/Oncology
University of Utah, Department of Pediatrics and Primary Children’s Hospital, Salt Lake City, Utah, United States
Salt Lake City, Utah, United States

Co-Author(s)

Michael Wang, MD

HTC Clinical Director
University of Colorado Denver Hemophilia and Thrombosis Center
Aurora, Colorado, United States
JC

Julie Curtin

Senior Staff Specialist
The Children’s Hospital at Westmead, New South Wales, Australia
Westmead, New South Wales, Australia
AH

Angela Huth-Kuehne

Clinician
Kurpfalzkrankenhaus Heidelberg GmbH, Heidelburg, Germany
Heidelberg, Baden-Wurttemberg, Germany
LL

Lynda Mae Lepatan

Clinician
Perpetual Succour Hospital, Cebu, Philippines
Cebu City, Cebu, Philippines
Christoph Male, MD, MSc

Head of the Pediatric Hemostasis & Thrombosis Unit
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
Vienna, Wien, Austria
Flora Peyvandi, MD, PhD

Professor of Internal Medicine; Director of the Angelo Bianchi Bonomi Hemophilia & Thrombosis Center
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Milan, Lombardia, Italy
MV

Mario Von Depka Prondzinski

Medical Director
Werlhof Institute, Hannover, Germany
Hannover, Niedersachsen, Germany
WM

William McKeand

Clinical Pharmacologist
CSL Behring, King of Prussia, United States
King of Prussia, Pennsylvania, United States
WS

Wilfried Seifert

Director Clinical Development
CSL Behring, Marburg, Germany
Marburg, Hessen, Germany
JO

Johannes Oldenburg

Director of the Institute of Experimental Haematology and Transfusion Medicine
University Clinic Bonn, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Berlin, Germany

Background: Recombinant fusion protein linking coagulation factor IX (FIX) with albumin (rIX-FP) has been shown to be efficacious and well tolerated with prolonged dosing intervals of up to 21 days in previously treated patients.

Aims: This study evaluated the safety and efficacy of prophylaxis with rIX-FP in previously untreated patients (PUPs).

Methods: PUPs with severe/moderately severe hemophilia B (FIX ≤2%) who had never been treated with FIX products received weekly rIX-FP prophylaxis (25–50 IU/kg, up to a maximum of 75 IU/kg) over ≥ 50 exposure days (EDs). Primary outcomes were the safety of rIX-FP, including the development of FIX inhibitors, and pharmacokinetic (PK) parameters. Secondary outcomes included total annualized and spontaneous bleeding rates (ABR and AsBR).

Results: Twelve PUPs with a mean (range) age of 1.3 (0-11) years received routine prophylaxis. Mean (SD) exposure to rIX-FP was 68.3 (38.0) EDs. One 11-year-old PUP (8.3%, 95% CI 1.5–35.4) developed an inhibitor against FIX after eight EDs which was recorded as a related serious adverse event (AE) and the patient was discontinued from the study. Most treatment-emergent AEs were unrelated to rIX-FP and mild or moderate in intensity (Table 1).
PK parameters were evaluated in 8 PUPs after a single infusion of 50 IU/kg rIX-FP (Table 2). The mean steady-state FIX activity trough was >10%.
In the 12 PUPs on the routine prophylaxis regimen, total ABR ranged from 0 to 3.89. Nine PUPs had an AsBR of 0. Six PUPs reported a total of 23 joint bleeding episodes; 13 episodes were reported in the PUP that had developed an inhibitor to FIX. Across all treatments, 93.8% of spontaneous bleeding events were successfully controlled with 1 or 2 rIX-FP infusions.

Conclusion(s): This study confirmed the safety and efficacy of rIX-FP when used for routine prophylaxis and on-demand treatment in pediatric PUPs.