Phase 3 Study of Recombinant Factor IX Fc Fusion Protein in Hemophilia B

• Published in: The New England journal of medicine Vol. 369; no. 24; pp. 2313 - 2323
• Main Authors: Powell, Jerry S, Pasi, K. John, Ragni, Margaret V, Ozelo, Margareth C, Valentino, Leonard A, Mahlangu, Johnny N, Josephson, Neil C, Perry, David, Manco-Johnson, Marilyn J, Apte, Shashikant, Baker, Ross I, Chan, Godfrey C, Novitzky, Nicolas, Wong, Raymond S, Krassova, Snejana, Allen, Geoffrey, Jiang, Haiyan, Innes, Alison, Li, Shuanglian, Cristiano, Lynda M, Goyal, Jaya, Sommer, Jurg M, Dumont, Jennifer A, Nugent, Karen, Vigliani, Gloria, Brennan, Aoife, Luk, Alvin, Pierce, Glenn F
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 12.12.2013
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Bleeding; Body weight; Child; Coagulation factors; Factor IX - adverse effects; Factor IX - pharmacokinetics; Factor IX - therapeutic use; Factor IX deficiency; Fc receptors; Female; Fusion protein; General aspects; Half-Life; Hematologic and hematopoietic diseases; Hemophilia; Hemophilia B - drug therapy; Hemophilia B - metabolism; Hemorrhage - prevention & control; Hemostasis; HIV; Human immunodeficiency virus; Humans; Male; Medical research; Medical sciences; Middle Aged; Patients; Pharmacokinetics; Platelet diseases and coagulopathies; Prophylaxis; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - therapeutic use; Young Adult; Medicine; Factor IX; Hemophilia B; Hemopathy; Fusion protein; Coagulopathy; Genetic disease
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1305074

A fusion protein comprising factor IX and the dimeric Fc domain of IgG1 has a half-life that is five times as long as that of native factor IX, allowing prophylactic injections to be spaced as far as 2 weeks apart while maintaining levels of factor IX that are sufficient to prevent bleeding. In patients with severe hemophilia B, recurrent bleeding leads to painful hemarthroses, disabling hemophilic arthropathy, and other sequelae. 1 , 2 Prophylactic replacement of coagulation factor IX is associated with improved clinical outcomes 3 – 7 ; however, the relatively short half-lives of currently available factor IX products necessitate frequent intravenous injections (two or three times weekly) to maintain protective levels (at or above 1 IU per deciliter). 8 , 9 The frequency of injections is a considerable burden, cited by patients as a key deterrent to undertaking prophylactic treatment. 10 Various strategies to reduce this burden and improve the treatment of hemophilia B are under investigation, . . .