Semin Thromb Hemost 2016; 42(05): 526-532
DOI: 10.1055/s-0036-1571310
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Innovative Pharmacological Therapies for the Hemophilias Not Based on Deficient Factor Replacement

Pier Mannuccio Mannucci
1  Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
,
Maria Elisa Mancuso
1  Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
,
Elena Santagostino
1  Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
,
Massimo Franchini
2  Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantova, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
05 May 2016 (online)

Abstract

In recent years, advances in the pharmacological treatment of hemophilias A and B have mainly focused on the development of long-acting factor (F)VIII and FIX products. Alternative approaches not based on the replacement of the missing factor have also been explored, with the aim of producing therapeutic agents with reduced immunogenicity and yet equally effective in patients with or without inhibitors. These new classes of hemostatic agents act mainly by bypassing the need of FVIII and FIX in tenase formation, quenching anticoagulant pathways, enhancing the activity of some coagulation factors or stabilizing the fibrin clot. Current knowledge on the status of development of these novel molecules is summarized in this narrative review. We also surmise that the main interests for these products not based on the replacement of FVIII or FIX in deficient patients pertain to the potential for bleeding prevention in inhibitor patients, an earlier and easier prophylaxis implementation thanks to subcutaneous administration and prolonged half-life, and a low immunogenicity with the potential for prevention of inhibitor development in high-risk patients.

Note

A new long-acting pegylated factor VIII produced by Baxalta is now licensed. A phase 1 study of ACE 910 in healthy subjects is now published in full.[59] The compound at doses up to 1 mg/kg was well tolerated and had no notable adverse hypercoagulable effect in 64 subjects.