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

Richard Lemons; Michael Wang; Julie Curtin; Lynda Mae Lepatan; Christoph Male; Flora Peyvandi; Mario von Depka Prondzinski; Rongrong Wang; William McKeand; Wilfried Seifert; Johannes Oldenburg

doi:10.1055/s-0044-1781466

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

TH Open. 2024 Mar 26;8(1):e155-e163. doi: 10.1055/s-0044-1781466. eCollection 2024 Jan.

Authors

Affiliations

¹ Department of Pediatrics and Primary Children's Hospital, University of Utah, Salt Lake City, Utah, United States.
² Hemophilia and Thrombosis Center, University of Colorado School of Medicine, Colorado, United States.
³ The Children's Hospital at Westmead, New South Wales, Australia.
⁴ Department of Health Research and Pediatrics, Cebu Normal University-Vicente Sotto Memorial Medical Center College of Medicine, Cebu, Philippines.
⁵ Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
⁶ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.
⁷ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
⁸ Werlhof Institute, Hannover, Germany.
⁹ CSL Behring, King of Prussia, Pennsylvania, United States.
¹⁰ CSL Behring, Marburg, Germany.
¹¹ Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Germany.

Abstract

Introduction Recombinant fusion protein linking coagulation factor IX (FIX) with albumin (rIX-FP) has been shown to be an effective, well-tolerated treatment for patients with severe hemophilia B who had previously received factor replacement therapy. This study investigated the safety and efficacy of rIX-FP in previously untreated patients (PUPs). Methods Patients with moderately severe/severe hemophilia B (≤2% FIX) previously untreated with FIX replacement products received rIX-FP (25-75 IU/kg) prophylaxis weekly or on-demand treatment over ≥50 exposure days (EDs). Primary outcomes were the number of patients who developed FIX inhibitors and mean incremental recovery (IR) following a 50 IU/kg dose of rIX-FP. Secondary outcomes included incidence of adverse events (AEs) and annualized bleeding rates (ABRs). Results In total, 12 PUPs with a median age of 0 years (range, 0-11 years) were treated with rIX-FP for a median of 50 EDs (6/12 prophylaxis; 6/12 on-demand then prophylaxis). Overall, 11/12 patients did not develop FIX inhibitors; one 11-year-old patient developed an inhibitor against FIX after 8 EDs and was ultimately withdrawn. Mean (standard deviation) IR was 1.2 (0.4, n = 8) (IU/dL)/(IU/kg). Of the 137 treatment-emergent AEs recorded, five were attributed to rIX-FP. On the prophylaxis regimen, median ABR was 1.0 (range, 0-3.9, n = 12). No thromboembolic events or deaths occurred during the study. Conclusion This study provides data to support the safety and efficacy of rIX-FP in PUPs requiring on-demand or prophylactic treatment for moderately severe/severe hemophilia B, consistent with results in previously treated patients. Overall, 1/12 patients developed an inhibitor against FIX.

Keywords: factor IX; hemophilia B; pediatric; previously untreated patients; prophylaxis.

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