Novel products for haemostasis - current status.
Currently, new clotting factor concentrates are becoming available or are in advanced clinical studies that will significantly improve the treatment of patients with Haemophilia A or Haemophilia B. Various technologies are applied to extend half-life and/or allow for alternative routes of administration, e.g. subcutaneous route. Today, the advances for recombinant factor IX are significantly with half-life extensions to up to 100 h, allowing substitution intervals of 1-2 weeks. For recombinant factor VIII (FVIII) products the effect so far is only moderate, as the half-life extension is limited to about 15-18 h by the clearance of FVIII through its binding to von Willebrand factor. However, novel products applying new technologies with significantly extended half-life are already at the horizont, as a bispecific antibody that mimics FVIII. The pharmacokinetic improvements of the new products will lead to a revision of our current treatment regimens, with regard to intended trough levels, number of tolerated bleeds and likely will drive a greater individualization of regimens. Clearly, the potential of anti drug antibody response for these modified proteins must not be higher than with our current products. Another challenge are the increasingly diverse biochemical characteristics of the new products, that have to be considered when determining potencies and also when monitoring treatment in patients with the various available assays. Despite these challenges, the new products will significantly improve treatment and quality of life for our patients with haemophilia.
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
J
J
Oldenburg
T
T
Albert
D000818:Animals; D000911:Antibodies, Monoclonal; D058833:Antithrombin Proteins / Q000235:genetics; D000991:Antithrombins; D001709:Biotechnology; D001779:Blood Coagulation Factors / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005164:Factor IX; D005169:Factor VIII; D015942:Factor VIIa; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015202:Protein Engineering; D034622:RNA Interference; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058833:Antithrombin Proteins; D000991:Antithrombins; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D005169:Factor VIII; D005164:Factor IX; D015942:Factor VIIa
haemophilia; half-life; long-acting clotting factor; novel products; pharmacokinetic