Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

• Published in: Blood Vol. 120; no. 12; pp. 2405 - 2411
• Main Authors: Santagostino, Elena, Negrier, Claude, Klamroth, Robert, Tiede, Andreas, Pabinger-Fasching, Ingrid, Voigt, Christine, Jacobs, Iris, Morfini, Massimo
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 20.09.2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Adult; Albumins - metabolism; Biological and medical sciences; Clinical Trials and Observations; Factor IX - metabolism; Female; Hematologic and hematopoietic diseases; Hemophilia B - metabolism; Hemophilia B - therapy; Humans; Infusions, Intravenous; Male; Medical sciences; Platelet diseases and coagulopathies; Prognosis; Prospective Studies; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - therapeutic use; Safety; Thrombosis and Hemostasis; Tissue Distribution; Human; Hematology; Albumin; Hemophilia B; Hemopathy; Protein A; Genetic disease; Factor IX; Recombinant protein; Pharmacokinetics; Fusion protein; Coagulation factor; Coagulopathy
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-05-429688

A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatment-related adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440.