Hemlibra SC Injection

Hemlibra is a bispecific factor IXa- and factor X-directed antibody indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors.

Emicizumab mimics the function of coagulation factor VIII, therefore it binds to the activated form of Factor IX (Factor IXa). This binding forms a complex that will later bind to the X factor of the coagulation factor. The ability of Emicizumab to interact with both factors (Factor IXa and Factor X) activates the coagulation cascade that will subsequently lead to the segmentation of fibrinogen into fibrin and the formation of blood clots. The effect of Emicizumab is translated into the restoration of the blood coagulation process and, therefore, in the reduction of hemorrhagic episodes. The activity of emicizumab can also produce changes in activated clotting time (ACT), activated partial thromboplastin time (aPTT) and one-step Factor VIII activity. In addition, the unique bispecific structure of Emicizumab prevents the formation of Factor VIII inhibitors or their effect.

Emicizumab exerts its action by performing the function of the coagulation Factor VIII without presenting a structural homology. It presents a dual specificity which allows it to bind to both the Factor IXa and Factor X, performing the required bridging activity for the launch of the coagulation cascade.

Recommended loading dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by a maintenance dose of:

• 1.5 mg/kg once every week, or
• 3 mg/kg once every two weeks, or
• 6 mg/kg once every four weeks.

Hypercoagulability with Concomitant Use of aPCC: Clinical experience suggests that a drug interaction exists with Hemlibra and aPC.

The following serious adverse reactions are described:

• Thrombotic Microangiopathy Associated with HEMLIBRA and aPCC
• Thromboembolism Associated with HEMLIBRA and aPCC
• Immunogenicity

Pregnancy: There are no available data on emicizumab use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies have not been conducted with emicizumab-kxwh. It is not known whether emicizumab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Emicizumab should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation: There is no information regarding the presence of emicizumab-kxwh in human milk, the effects on the breastfed child, or the effects on milk production. Human IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for emicizumab and any potential adverse effects on the breastfed child from emicizumab or from the underlying maternal condition.

Immunogenicity: Anti-Hemlibra antibodies (including neutralizing antibodies) have developed in Hemlibra-treated patients. In case of clinical signs of loss of efficacy, promptly assess the etiology and consider a change in treatment if neutralizing antibodies are suspected.

Laboratory Coagulation Test Interference: Hemlibra interferes with activated clotting time (ACT), activated partial thromboplastin time (aPTT), and coagulation laboratory tests based on aPTT, including one-stage aPTT-based single-factor assays, aPTT-based Activated Protein C Resistance (APC-R), and Bethesda assays (clotting-based) for factor VIII (FVIII) inhibitor titers. Intrinsic pathway clotting-based laboratory tests should not be used.

Store Hemlibra vials in a refrigerator at 2°C to 8°C in the original carton to protect from light. Do not freeze. Do not shake. Prior to administration, if needed, unopened vials of Hemlibra may be stored out of and then returned to refrigeration. The temperature and total combined time out of refrigeration should not exceed 30°C and 7 days (at a temperature below 30°C, respectively. Once removed from the vial, discard Hemlibra if not used immediately.