title: Emerging drugs for hemophilia B.
abstract: BACKGROUND
  Hemophilia B is a rare congenital bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). Hemophilia B patients experience mild-to-severe bleeding complications according to the degree of FIX defect. Prophylaxis, with regular infusion of FIX concentrates, is nowadays, the mainstay of hemophilia care. However, because the relatively short half-life of such products necessitates frequent infusions and thus makes patients' adherence difficult, a number of strategies have been implemented to improve the pharmacokinetics of FIX clotting factors.
  
  
  METHODS
  This review summarizes the main results of Phase I/II and III studies on new FIX molecules engineered to have a longer half-life. Several technologies are being applied to extend FIX half-life, including Fc fusion, recombinant (r) albumin fusion and the addition of PEG polymers.
  
  
  CONCLUSIONS
  By prolonging the FIX half-life up to 5 times, long-acting FIX products are expected to substantially improve the management of hemophilia B patients, allowing less frequent infusions and improving patients' adherence to prophylactic regimens and individualized treatments. Some of them are at an advanced stage of development, such as the rFIX-Fc which has been launched in March 2014. Along with the ongoing Phase III trials, long-term post-marketing surveillance studies are needed to assess their safety and effectiveness and their impact on patients' quality of life.
authors.affiliation: IRCCS Cà Granda Foundation Maggiore Policlinico Hospital, Scientific Direction , Via Pace 9, 20122 Milan , Italy +39 02 55038377 ; +39 02 50320723 ; piermannuccio.mannucci@policlinico.mi.it.
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D015195:Drug Design; D005164:Factor IX / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D055118:Medication Adherence; D011788:Quality of Life; D012720:Severity of Illness Index
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D005164:Factor IX
keywords: factor IX; factor IX concentrates; hemophilia B; prolonged half-life