The therapeutic approach to genetic bleeding disorders has had a big and rapid evolution since the second half of the XX century thanks to the production of the first plasma-derived concentrate of coagulation factor. However, the lack of viral inactivation procedures of the concentrates, and the lack of knowledge about the possibility of transmission of viral agents using the same, has caused in the population of hemophilic patients epidemic of HIV and HCV-relate infection . From 1985 onwards, the concentrated plasma derivatives are subjected to viral inactivation techniques, also combined with increasingly effective technology. In addition, the accurate viral donor screening tests become widely available using led to the disappearance of new infections by the most feared pathogens. Moreover, the possibility of transmitting agents such as parvovirus B19, also low pathogenic, or prions, associated with Creutzfeldt-Jakob disease, are reasons to maintain high surveillance of plasma-derived products. There could be also the possibility that micro-organisms responsible for outbreaks of viral haemorrhagic fevers in Africa, or West Nile virus can be transmit through blood. Since 1990, the concentrates obtained in recombinant cell culture thanks to the techniques of recombinant DNA and subjected to multiple purification steps and in the treatment of viral inactivation have conferred the advantage of an almost absolute security of not transmitting viral infections.

Prophylaxis with emicizumab in hemophiliacs A without inhibitor

Emicizumab represents a therapeutic innovation not only for haemophiliacs A with inhibitor but also for those without inhibitor. This is what the recently published Haven 3 study has shown. Thephase 3 study was performed on 152 enrolled patients aged ≥ 12 years and randomly assigned witha 2: 2: 1 ratio in 4 groups in order […]

A promising approach for treatment of severe hemophilia A patients with inhibitor.

Current standard therapy for severe hemophilia A is regular infusions of either plasma-derived or recombinant factor VIII (FVIII) for prophylaxis and for treating bleeding episodes when they occur (“on demand” therapy). Nowadays the most important complication of replacement therapy is that a significant number of patients develop neutralizing alloantibodies (inhibitors) against exogenous FVIII. Inhibitors are […]

Brief report on gene therapy for severe hemophilia

Patients affected by severe hemophilia A and B must be treated with plasmaderived or recombinant factor replacement with significant improvement in morbidity and mortality, as well as in their quality of life. Nowadays prophylaxis represents the golden standard for the management of hemophilia, using fixed doses of factor VIII/factor IX (FVIII/FIX) concentrates at fixed timing […]

Recent innovations in replacement and no-replacement therapy of hemophilia

The most important and prevalent inherited bleeding disorders are hemophilia A and B, rare recessive X-linked diseases  (1/5.000 and 1/30.000 male respectively). The severity of disesase is based on the levels of factor VIII (FVIII) and factor IX (FIX) into the bloodstream: <1% (severe type), 1 to 5% (moderate type), >5 to <40% (mild type). […]

A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects

ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to […]