Altuviiio (antihemophilic factor rFVIII Fc-VWF-XTEN,BDD-ehtl)

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is a biosynthetic (recombinant DNA origin) preparation of blood coagulation factor VIII consisting of a single chain B-domain-deleted factor VIII covalently linked to the Fc domain of human immunoglobulin G (IgG), the FVIII-binding D'D3 domain of human von Willebrand factor (VWF), and 2 XTEN polypeptides.

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is a biosynthetic (recombinant DNA origin) preparation of blood coagulation factor VIII consisting of a single molecule of B-domain-deleted human coagulation factor VIII covalently linked to the Fc domain of human immunoglobulin G1 (IgG1), the FVIII-binding D'D3 domain of human von Willebrand factor (VWF), and 2 XTEN polypeptides. The Fc, VWF, and XTEN polypeptide portions of the molecule prolong the half-life of factor VIII in plasma. Clinical studies have shown that the half-life of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is approximately 3- to 4-fold longer than that of currently available standard products and preparations of antihemophilic factor (recombinant).

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is a recombinant FVIII analogue fusion protein that is independent of endogenous VWF in order to overcome the half-life limit imposed by FVIII-VWF interactions. Because the D'D3 domain of VWF is the region that interacts with FVIII, appending the D'D3 domain of VWF to a recombinant FVIII-Fc fusion protein provides protection and stability to FVIII, and prevents FVIII interaction with endogenous VWF. The Fc region of human IgG1 binds to the neonatal Fc receptor(FcRn).

FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by recycling them back into circulation, thus prolonging the plasma half-life of the fusion protein. Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl contains 2 XTEN polypeptides, which alter the hydrodynamic radius of the fusion protein, thus reducing rates of clearance and degradation, and improving pharmacokinetic properties. Administration of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl increases plasma levels of FVIII, temporarily correcting the coagulation defect in hemophilia A patients.

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl (Altuviiio(R)) is produced by recombinant DNA technology in a human embryonic kidney (HEK) cell line and undergoes a series of purification and viral inactivating/removal processes. The factor product is manufactured without the addition of human- or animal-derived components. Compared with plasma-derived antihemophilic factor preparations, recombinant preparations of antihemophilic factor are associated with a substantially reduced risk of transmission of bloodborne human viruses (e.g., human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV)).

Following administration of a single 50-unit/kg dose of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl given as an IV injection in adults and adolescents with hemophilia A, the terminal half-life of the drug was approximately 48.2 hours in adults and 44.6 hours in adolescents (>12 to 18 years of age). The average time to reach mean factor VIII activity of more than 40 IU per deciliter was approximately 4 days in adults and 3.6 days in adolescents. The FVIII activity over 10 IU/dL was maintained in 83.5% of adults and adolescents throughout the study.

In children 6 to <12 years of age and children 1 to <6 years of age, the terminal half-life of the drug was approximately 42.4, and 38.0 hours, respectively, following administration of a single 50-unit/kg dose of the drug. In children <12 years of age, antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl maintained normal to near normal (>40 IU/dL) FVIII activity for 2 to 3 days and >10 IU/dL FVIII activity for approximately 7 days.

USES: This medication is used to control and prevent bleeding that happens to people (usually males) with an inherited medical condition, hemophilia A (low levels of factor VIII). It is also given before surgery to prevent too much bleeding in people with this condition. Factor VIII is a protein (clotting factor) that is in normal blood, and helps form blood clots and stop bleeding after an injury.

People with low factor VIII levels may bleed longer than normal after an injury/surgery and may have bleeding inside the body (especially in the joints and muscles). This medication contains man-made factor VIII (antihemophilic factor) to temporarily replace factor VIII in the body, connected to an antibody (immunoglobulin) that helps the man-made factor VIII work longer. When used to control and prevent bleeding, this medication may help relieve pain and long-term damage caused by hemophilia A.

This medication should not be used to treat von Willebrand disease.

Generic name: antihemophilic factor rFVIII Fc-VWF-XTEN,BDD-ehtl
Pronunciation: (AN-tye-HEE-moe-FIL-ik FAK-tor)
Drug class: Antihemophilic Products
Therapeutic class: Hematological Agents

The following indications are listed for Altuviiio:

• Bleeding Episode In Hemophilia A
• Bleeding Prevention In Hereditary Factor Viii Deficiency
• Hemophilia A

Also known as: Bleeding Prevention In Classic Hemophilia, Bleeding Prevention In Congenital Factor Viii Deficiency, Bleeding Prevention In Hemophilia A, Bleeding Prophylaxis In Hemophilia A, Congenital Factor Viii Deficiency Disease, Hemorrhage Prophylaxis In Hemophilia A, Hemorrhaging In Hemophilia A, Prevention Of Bleeding Episode In Hemophilia A.