title: Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B.
abstract: BACKGROUND
  Prophylactic factor replacement in patients with hemophilia B improves outcomes but requires frequent injections. A recombinant factor IX Fc fusion protein (rFIXFc) with a prolonged half-life was developed to reduce the frequency of injections required.
  
  
  METHODS
  We conducted a phase 3, nonrandomized, open-label study of the safety, efficacy, and pharmacokinetics of rFIXFc for prophylaxis, treatment of bleeding, and perioperative hemostasis in 123 previously treated male patients. All participants were 12 years of age or older and had severe hemophilia B (endogenous factor IX level of ≤2 IU per deciliter, or ≤2% of normal levels). The study included four treatment groups: group 1 received weekly dose-adjusted prophylaxis (50 IU of rFIXFc per kilogram of body weight to start), group 2 received interval-adjusted prophylaxis (100 IU per kilogram every 10 days to start), group 3 received treatment as needed for bleeding episodes (20 to 100 IU per kilogram), and group 4 received treatment in the perioperative period. A subgroup of group 1 underwent comparative sequential pharmacokinetic assessments of recombinant factor IX and rFIXFc. The primary efficacy end point was the annualized bleeding rate, and safety end points included the development of inhibitors and adverse events.
  
  
  RESULTS
  As compared with recombinant factor IX, rFIXFc exhibited a prolonged terminal half-life (82.1 hours) (P<0.001). The median annualized bleeding rates in groups 1, 2, and 3 were 3.0, 1.4, and 17.7, respectively. In group 2, 53.8% of participants had dosing intervals of 14 days or more during the last 3 months of the study. In groups 1, 2 and 3, 90.4% of bleeding episodes resolved after one injection. Hemostasis was rated as excellent or good during all major surgeries. No inhibitors were detected in any participants receiving rFIXFc; in groups 1, 2, and 3, 73.9% of participants had at least one adverse event, and serious adverse events occurred in 10.9% of participants. These events were mostly consistent with those expected in the general population of patients with hemophilia.
  
  
  CONCLUSIONS
  Prophylactic rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov number, NCT01027364.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Powell
authors.forename: K John
authors.initials: KJ
authors.lastname: Pasi
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
authors.forename: Margareth C
authors.initials: MC
authors.lastname: Ozelo
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Valentino
authors.forename: Johnny N
authors.initials: JN
authors.lastname: Mahlangu
authors.forename: Neil C
authors.initials: NC
authors.lastname: Josephson
authors.forename: David
authors.initials: D
authors.lastname: Perry
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Manco-Johnson
authors.forename: Shashikant
authors.initials: S
authors.lastname: Apte
authors.forename: Ross I
authors.initials: RI
authors.lastname: Baker
authors.forename: Godfrey C
authors.initials: GC
authors.lastname: Chan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Novitzky
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Wong
authors.forename: Snejana
authors.initials: S
authors.lastname: Krassova
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Allen
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Alison
authors.initials: A
authors.lastname: Innes
authors.forename: Shuanglian
authors.initials: S
authors.lastname: Li
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Cristiano
authors.forename: Jaya
authors.initials: J
authors.lastname: Goyal
authors.forename: Jurg M
authors.initials: JM
authors.lastname: Sommer
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Dumont
authors.forename: Karen
authors.initials: K
authors.lastname: Nugent
authors.forename: Gloria
authors.initials: G
authors.lastname: Vigliani
authors.forename: Aoife
authors.initials: A
authors.lastname: Brennan
authors.forename: Alvin
authors.initials: A
authors.lastname: Luk
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Pierce
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005164:Factor IX / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy* / Q000378:metabolism; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D011993:Recombinant Fusion Proteins; D005164:Factor IX