title: Investigational drugs for coagulation disorders.
abstract: BACKGROUND
  The current standard treatment in persons with hemophilia (PWH) is prophylaxis, given intravenously twice or thrice weekly, which is associated with a non negligible burden on patients' quality of life. Therefore the main attempts aiming to improve the management of PWH are targeted towards the development of a new generation of coagulation factors endowed with properties facilitating prophylaxis and/or a better control of bleeding.
  
  
  METHODS
  This article summarizes the main results obtained so far in the development of new antihemophilic products, and emphasizes the formidable requirements imposed upon by regulatory agencies to get marketing authorization for new drugs, which make progress in this field difficult. Published literature on new molecules for replacement treatment in hemophilia A and B has been retrieved by using PubMed search and all ongoing clinical trials have been looked for online.
  
  
  CONCLUSIONS
  New molecules are usually engineered to have a longer plasma half-life but also in some instances a higher potency. The prolongation of half-life may be obtained by using sustained release delivery vehicles, by chemical modification or by creating fusion proteins. Factors VIII, IX and VII have been variably modified in order to obtain improved coagulation products and results from Phase I/II studies are encouraging, particularly for factor IX. However, Phase III studies that should provide evidence on efficacy and effectiveness more cogent for clinical use are still ongoing and results are not yet available.
authors.affiliation: Scientific Direction and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, Via Pace 9, 20122 Milano, Italy. piermannuccio.mannucci@policlinico.mi.it
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Mancuso
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans
chemical_list: D001779:Blood Coagulation Factors; D015507:Drugs, Investigational