Recombinant factor VIII in the management of hemophilia A: current use and future promise

Abstract

Hemophilia A is a rare inherited bleeding disorder due to mutation of the gene that encodes the coagulation protein factor VIII. Historically, prior to the availability of treatment with factor VIII preparations, most boys died from uncontrolled bleeding, either spontaneous bleeding or after injury, before reaching 20 years of age. One of the most impressive triumphs of modern medicine is that with current recombinant factor VIII replacement therapy, a boy born in the 21st century with severe hemophilia A can anticipate a normal life expectancy with essentially no permanent complications from bleeding. For severe hemophilia A, current optimal treatment should have two goals: first, to provide sufficient factor VIII to prevent spontaneous bleeding, and second, to provide sufficient factor VIII to have normal coagulation function after any trauma. However, the replacement therapy requires tremendous resources for effective use, and remains extraordinarily expensive. Thus there are opportunities for further advances in therapy for hemophilia A. Two major concerns continue to trouble current optimal treatment approaches: some patients will develop neutralizing antibodies during the first 50 infusions of therapeutic factor VIII, and second, to administer therapeutic factor VIII every other day in young boys often requires placement of a central venous access device, and such use carries the life-threatening risks of infection and thrombosis. Because of the effectiveness of current therapy, any new developments in treatment will require significant concerns for safety, both immediate and in the long term. A number of research groups seek to prolong the biological efficacy of infused recombinant factor VIII. Currently, one such promising development is in the advanced stages of clinical trial. The goals will be to improve further the quality of life of an individual with severe hemophilia A, and to reduce the burden of current treatment strategies on families and medical resources. Hopefully, the hemophilia community will continue to participate actively in the clinical trials needed to address these new challenges.

Native Molecular State of Adeno-Associated Viral Vectors Revealed by Single-Molecule Sequencing

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Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors

“…7,14 In infants, the need for frequent IV access can prove particularly difficult, and central venous access devices are often required. 15 The development of FVIII inhibitors (anti-FVIII antibodies), which render FVIII replacement therapy ineffective, is 1 of the most challenging complications of treatment.…”

Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

“…Intravenous FVIII replacement given prophylactically is the current standard of care for persons with haemophilia A (PwHA). However, due to short FVIII half‐life, regular intravenous infusions (2‐4 times/wk) are required to maintain protective trough levels and achieve adequate haemostatic coverage . Despite regular FVIII prophylaxis, clinical and subclinical bleeds may occur .…”