title: Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.
abstract: A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy;
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: The Israeli National Haemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel;
authors.forename: Uri
authors.initials: U
authors.lastname: Martinowitz
authors.affiliation: Department of Coagulation Disorders and Anemia, Specialized Hospital for Active Treatment Joan Pavel, Sofia, Bulgaria;
authors.forename: Toshko
authors.initials: T
authors.lastname: Lissitchkov
authors.affiliation: Centre Hospitalier Régional Universitaire de Brest, Hôpital A. Morvan, Brest, France;
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pan-Petesch
authors.affiliation: Department of Hematology, Ogikubo Hospital, Tokyo, Japan;
authors.forename: Hideji
authors.initials: H
authors.lastname: Hanabusa
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Rush Hemophilia and Thrombophilia Center, Rush University, Chicago, IL;
authors.forename: Lisa
authors.initials: L
authors.lastname: Boggio
authors.affiliation: Centre Régional de Traitement de l'Hémophilie, Hôpital Edouard Herriot, University Claude Bernard, Lyon, France;
authors.forename: Claude
authors.initials: C
authors.lastname: Negrier
authors.affiliation: Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Werlhof Institut, Hannover, Germany;
authors.forename: Mario
authors.initials: M
authors.lastname: von Depka Prondzinski
authors.affiliation: Unitat Hemofilia, Hospital Vall d'Hebron, Barcelona, Spain;
authors.forename: Carmen
authors.initials: C
authors.lastname: Altisent
authors.affiliation: Haemophilia and Thrombosis Centre, Department of Haematology, San Bortolo Hospital, Vicenza, Italy; Center for Bleeding Disorders, Careggi University Hospital, Florence, Italy;
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.affiliation: Nagoya University Hospital, Nagoya, Japan;
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Hospital la Paz, Madrid, Spain; and.
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Álvarez-Roman
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA.
authors.forename: Christine
authors.initials: C
authors.lastname: Voigt
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Blackman
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA.
authors.forename: Iris
authors.initials: I
authors.lastname: Jacobs
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D005164:Factor IX / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002836:Hemophilia B / Q000097:blood* / Q000473:pathology / Q000517:prevention & control*; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000418:Albumins; D011993:Recombinant Fusion Proteins; D005164:Factor IX