From the Guidelines
Emicizumab (brand name Hemlibra) is a bispecific monoclonal antibody medication used to prevent or reduce bleeding episodes in patients with hemophilia A, particularly those who have developed inhibitors to factor VIII replacement therapy. The standard dosing regimen begins with a loading dose of 3 mg/kg subcutaneously once weekly for the first four weeks, followed by a maintenance dose of either 1.5 mg/kg weekly, 3 mg/kg every two weeks, or 6 mg/kg every four weeks, as supported by recent guidelines 1. Emicizumab works by mimicking the function of activated factor VIII, bringing together factors IXa and X to restore the blood clotting process that is impaired in hemophilia A patients, as described in the clinical practice guideline for treatment of congenital hemophilia A and B 1. This mechanism is effective regardless of the presence of factor VIII inhibitors, making it particularly valuable for patients who have developed resistance to traditional factor VIII replacement therapy. Common side effects include injection site reactions, headache, and arthralgia, and patients should be monitored for thrombotic events and should avoid concurrent use of activated prothrombin complex concentrate when possible, as this combination has been associated with thrombotic microangiopathy and thromboembolism 1. The use of emicizumab may offer a lower treatment burden for patients given its weekly, biweekly, or every 4-week schedule and subcutaneous administration, as noted in the international society on thrombosis and haemostasis clinical practice guideline 1. Key considerations in the management of patients with hemophilia A include the potential for inhibitor development, the role of prophylaxis, and the selection of appropriate antithrombotic therapy, as discussed in the guideline for treatment of congenital hemophilia A and B 1. Overall, emicizumab is a valuable treatment option for patients with hemophilia A, particularly those with inhibitors, and its use should be guided by current clinical practice guidelines and individual patient needs.
From the FDA Drug Label
Emicizumab-kxwh is a humanized monoclonal modified immunoglobulin G4 (IgG4) bispecific antibody binding factor IXa and factor X. Emicizumab-kxwh has an approximate molecular weight of 145.6 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. Emicizumab-kxwh has no structural relationship or sequence homology to FVIII and, as such, does not induce or enhance the development of direct inhibitors to FVIII
Emicizumab (Hemlibra, generic name: emicizumab-kxwh) is a humanized monoclonal modified immunoglobulin G4 (IgG4) bispecific antibody that binds factor IXa and factor X to restore the function of missing activated factor VIII for effective hemostasis 2.
From the Research
Emicizumab Overview
- Emicizumab, also known as Hemlibra, is a recombinant, humanized, bispecific monoclonal antibody that restores the function of missing activated factor VIII (FVIII) by bridging FIXa and FX to facilitate effective haemostasis in patients with haemophilia A 3.
- It is approved in several countries, including the USA, Japan, and the EU, for the routine prophylaxis of bleeding episodes in patients with haemophilia A with or without FVIII inhibitors 3, 4.
Mechanism of Action
- Emicizumab mimics the cofactor function of missing activated FVIII by bridging activated factor IX and factor X, thereby restoring hemostasis 5.
- It has a linear pharmacokinetics with an approximately 1-month half-life, and once-weekly to every-4-week subcutaneous administrations maintain effective trough concentrations throughout the dosing intervals 5.
Clinical Efficacy
- Emicizumab has been shown to significantly reduce annualized bleeding rates compared with no prophylaxis in adolescents and adults with haemophilia A with or without inhibitors 3.
- It has also been effective in preventing or substantially reducing bleeding in children with haemophilia A with or without inhibitors 3.
- Emicizumab has been associated with beneficial effects on health-related quality of life and health status, and is generally well tolerated 3, 6.
Special Considerations
- The concurrent use of emicizumab and activated prothrombin complex concentrate imposes a high risk of thrombotic microangiopathy and thromboembolic events, and should be avoided 4, 6.
- Patient selection for emicizumab treatment and special considerations on the practical situations, such as concomitant treatment by bypassing agents or clotting factor concentrates, should be carefully evaluated 6.