Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients

• Published in: Blood Vol. 119; no. 3; pp. 666 - 672
• Main Authors: Shapiro, Amy D., Ragni, Margaret V., Valentino, Leonard A., Key, Nigel S., Josephson, Neil C., Powell, Jerry S., Cheng, Gregory, Thompson, Arthur R., Goyal, Jaya, Tubridy, Karen L., Peters, Robert T., Dumont, Jennifer A., Euwart, Donald, Li, Lian, Hallén, Bengt, Gozzi, Peter, Bitonti, Alan J., Jiang, Haiyan, Luk, Alvin, Pierce, Glenn F.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 19.01.2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Clinical Trials and Observations; Factor IX - metabolism; Female; Half-Life; Hematologic and hematopoietic diseases; Hemophilia B - metabolism; Hemophilia B - therapy; Humans; Male; Medical sciences; Middle Aged; Platelet diseases and coagulopathies; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - therapeutic use; Safety; Thrombosis and Hemostasis; Young Adult; Human; Factor IX; Hematology; Phase I trial; Hemophilia B; Hemopathy; Recombinant protein; Fusion protein; Coagulopathy; Biological activity; Genetic disease; Prolonged
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-07-367003

Current factor IX (FIX) products display a half-life (t1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.