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Review
. 2017 Mar 28;6(4):39.
doi: 10.3390/jcm6040039.

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Maria Elisa Mancuso  1 , Elena Santagostino  2
Affiliations
Review

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Maria Elisa Mancuso et al. J Clin Med. .

Abstract

The development of a new generation of coagulation factors with improved pharmacokinetic profile will change the paradigm of treatment of persons with hemophilia (PWH). The standard treatment in PWH is represented by regular long-term prophylaxis that, given intravenously twice or thrice weekly, is associated with a not-negligible burden on patients' quality of life. The availability of drugs with improved pharmacokinetic profile may improve prophylaxis feasibility and protection against bleeding episodes. This article summarizes the main results obtained from clinical trials with modified factor VIII (FVIII) and factor IX (FIX) molecules. Published literature on new molecules for replacement treatment in hemophilia A and B was retrieved using PubMed search, and all ongoing clinical trials have been researched via www.clinicaltrials.gov. Such new molecules are usually engineered to have a longer plasma half-life than that which has been obtained by chemical modification (i.e., conjugation with polyethylene glycol, PEG) or by creating recombinant fusion proteins. Results from phase I/III studies in previously treated adults and children are now available for the vast majority of new products, including the results of their use in a surgical setting. On the contrary, trials involving previously untreated patients are still ongoing for all and results not yet available.

Keywords: Fc fusion; albumin fusion; extended half-life concentrates; glycopegylation; hemophilia A; hemophilia B; long-acting products; pegylation.

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Conflict of interest statement

M.E.M. received speaker and/or consultancy fees from Bayer Healthcare, Baxalta/Shire, CSL Behring, NovoNordisk, Pfizer, and Sobi/Biogen Idec. E.S. received research support from CSL Behring, unrestricted research grants from Novo Nordisk and Pfizer, and speaker and/or consultancy fees from Bayer Healthcare, Baxalta/Shire, Biotest, CSL Behring, Grifols, Kedrion, NovoNordisk, Octapharma, Pfizer, Roche, and Sobi/Biogen Idec.

References

    1. Darby S.C., Kan S.W., Spooner R.J., Giangrande P.L., Hill F.G., Hay C.R., Lee C.A., Ludlam C.A., Williams M. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood. 2007;110:815–825. doi: 10.1182/blood-2006-10-050435. - DOI - PubMed
    1. Soucie J.M., Nuss R., Evatt B., Abdelhak A., Cowan L., Hill H., Kolakoski M., Wilber N. Mortality among males with hemophilia: Relations with source of medical care. The Hemophilia Surveillance System Project Investigators. Blood. 2000;96:437–442. - PubMed
    1. Plug I., Van Der Bom J.G., Peters M., Mauser-Bunschoten E.P., De Goede-Bolder A., Heijnen L., Smit C., Willemse J., Rosendaal F.R. Mortality and causes of death in patients with hemophilia, 1992–2001: A prospective cohort study. J. Thromb. Haemost. 2006;4:510–516. doi: 10.1111/j.1538-7836.2006.01808.x. - DOI - PubMed
    1. Tagliaferri A., Rivolta G.F., Iorio A., Oliovecchio E., Mancuso M.E., Morfini M., Rocino A., Mazzucconi M.G., Franchini M., Italian Association of Hemophilia Centers Mortality and causes of death in Italian persons with haemophilia, 1990–2007. Haemophilia. 2010;16:437–446. - PubMed
    1. Manco-Johnson M.J., Abshire T.C., Shapiro A.D., Riske B., Hacker M.R., Kilcoyne R., Ingram J.D., Manco-Johnson M.L., Funk S., Jacobson L., et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N. Engl. J. Med. 2007;357:535–544. doi: 10.1056/NEJMoa067659. - DOI - PubMed

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