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Semin Thromb Hemost 2021; 47(01): 032-042
DOI: 10.1055/s-0040-1718887
Review Article

Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Insights from Pivotal and Extension Studies

Matteo Nicola Dario Di Minno
1   Department of Translational Medical Sciences, Federico II University, Naples, Italy
,
Alessandro Di Minno
2   Dipartimento di Farmacia, Università degli Studi di Napoli “Federico II,” Napoli, Italy
,
Ilenia Calcaterra
3   Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
,
Ernesto Cimino
3   Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
,
Francesco Dell'Aquila
3   Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
,
Massimo Franchini
4   Department of Haematology and Transfusion Medicine, “Carlo Poma” Hospital, Mantua, Italy
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Abstract

The development of enhanced half-life recombinant factor VIII (EHL-rFVIII) concentrates has improved the management of hemophilia. Furthermore, the chance of maintaining higher trough levels has allowed higher protection from bleeding and, in turn, improved safely performance for certain types of physical activity. The first technology used to improve the pharmacokinetic profile of factor VIII (FVIII) was fusion with the Fc domain of immunoglobulin G. More recently, conjugation to hydrophilic polymers of polyethylene glycol (PEG) has been demonstrated to prolong plasma half-life of FVIII by means of a reduction in clearance of the molecule due to steric hindrance by PEG covering the protein. Here we report results of a systematic review of pivotal studies on EHL-rFVIII concentrates. Significant heterogeneity is observed among different studies on EHL-rFVIII concentrates, and direct comparisons should be avoided. The annualized bleeding rate has ranged between 1.2 and 1.9 in different EHL-rFVIII concentrates, with a progressive further decrease during extension phases of pivotal studies. Zero bleeding was reported by 40 to 45% of patients. Overall, the emerging treatment options seem to be highly effective and safe, associated with a decreased dosing interval to twice weekly or less, which reduces, but does not entirely eliminate, the burden of treatment. Overall, further information is needed from real-life settings to permit differentiation between EHL-FVIII concentrates and for individualizing treatment.

Keywords

hemophilia - enhanced half-life recombinant FVIII concentrates - bleeding


Publication History

Article published online:
21 December 2020

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