title: Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients.
abstract: 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.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy. elena.santagostino@policlinico.mi.it
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.forename: Claude
authors.initials: C
authors.lastname: Negrier
authors.forename: Robert
authors.initials: R
authors.lastname: Klamroth
authors.forename: Andreas
authors.initials: A
authors.lastname: Tiede
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger-Fasching
authors.forename: Christine
authors.initials: C
authors.lastname: Voigt
authors.forename: Iris
authors.initials: I
authors.lastname: Jacobs
authors.forename: Massimo
authors.initials: M
authors.lastname: Morfini
mesh_terms: D000328:Adult; D000418:Albumins / Q000378:metabolism*; D005164:Factor IX / Q000378:metabolism*; D005260:Female; D002836:Hemophilia B / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012449:Safety; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D011993:Recombinant Fusion Proteins; D005164:Factor IX