Updates on Novel Non-Replacement Drugs for Hemophilia

Authors: Gualtierotti, R; Pasca, S; Ciavarella, A; Arcudi, S; Giachi, A; Garagiola, I; Suffritti, C; Siboni, SM; Peyvandi, F

Affiliations: Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy. Biomedical Sciences Department (DSB)/Medicine Department (DIMED) Padua University Hospital, 35131 Padua, Italy.

Publication: Pharmaceuticals (Basel, Switzerland); 2022 ; 15

Abstract: Over the last decade, the world of hemophilia has experienced an unprecedented therapeutic advance, thanks to the progress in bioengineering technologies, leading to the introduction of drugs with novel mechanisms of action based on restoring thrombin generation or coagulation factor VIII mimicking. Apart from the bispecific monoclonal antibody emicizumab, already approved for patients with severe hemophilia A with and without inhibitors, novel non- replacement drugs designed to reduce the treatment burden of patients with hemophilia A or B with or without inhibitors are undergoing evaluation in clinical trials. Thanks to their innovative mechanism of action and subcutaneous administration, these drugs promise to provide effective bleeding protection together with improved adherence and improve health-related quality of life for patients with hemophilia. On the other hand, rare thromboembolic events have been reported with some of these drugs and warrant continuous post-marketing surveillance and investigation of predisposing factors, although the overall safety profile of most of these drugs is good. Finally, new challenges need to be faced in the clinical and laboratory monitoring of the hemostatic status in patients treated with these innovative therapies. In this review, we provide an update on the available data on novel non-replacement drugs currently undergoing evaluation in clinical trials for patients with hemophilia.