Impact of novel hemophilia therapies around the world

Abstract

Essentials• Replacement therapy has been the standard of care for hemophilia since the late 1950s.• Emicizumab, the first nonfactor therapy for hemophilia A, changed the hemophilia care scenario.• Rebalancing agents and gene therapy are new options with ongoing studies and promising results.• The main challenge remains the same: guarantee treatment for all.

Immunogenicity of Current and New Therapies for Hemophilia A

“…Frequent intravenous infusion is considered a significant burden in hemophilia treatment, increasing the need for central venous catheters in young patients and compromising adherence, particularly in children and adolescents. To fulfill the unmet need for a user-friendly dosing scheme, clotting factor concentrates with EHL have been developed since the 2010s [ 59 , 60 ].…”

“…However, the new bioengineered molecules of FVIII have achieved a minor improvement in the half-life—only 1.5 to 1.8 times compared to SHL-rFVIII products. This modest improvement in FVIII pharmacokinetics (PK) parameters is probably due to the VWF half-life, which binds to FVIII in the circulation and protects FVIII from otherwise rapid clearance [ 60 ].…”

“…However, a significant improvement was recently achieved with the development of non-replacement therapies. This class of new agents aims to either restore the hemostasis using mimetic products or establish a unique balance of the hemostasis, thereby inhibiting the anticoagulant pathways [ 60 ].…”

“…Emicizumab is a humanized bispecific monoclonal antibody with binding sites to activated factor IX and factor X, mimicking the co-factorial activity of FVIII [ 74 ]. In addition, emicizumab is administered subcutaneously, dosing each 1, 2, or 4 weeks, thereby overcoming the burden associated with frequent intravenous injections, with the same effectiveness regardless of age [ 4 , 60 ].…”

Supporting patients with haemophilia in a world of crises: New role for the WFH and its partners

“…They concern the understanding of the mechanisms, diagnosis, treatment and care of clotting factor VIII and IX deficiencies and other inherited bleeding disorders 1 . These advances have recently culminated in the development of new treatments 2,3 and especially in the demonstration of the possibility of curing both haemophilia A and B by gene therapy in the future 4 . Apart from successes, these decades will also be remembered by failures and disasters, such as the infection and death of thousands of patients by factor concentrates containing HCV or HIV.…”