Esperoct (antihemophilic factor (FVIII) rec, B-dom truncated peg-exei)

Antihemophilic factor (recombinant), glycopegylated-exei is a biosynthetic (recombinant DNA origin) preparation of blood coagulation factor VIII conjugated with a polyethylene glycol (PEG) molecule.

Antihemophilic factor (recombinant), glycopegylated-exei, a glycopegylated form of recombinant antihemophilic factor, is a temporary replacement for coagulation factor VIII that provides hemostasis in patients with congenital hemophilia A. Since the factor VIII in antihemophilic factor (recombinant), glycopegylated-exei is conjugated to a 40-kDa polyethylene glycol (PEG) molecule, it has an increased half-life and decreased clearance compared to the non-pegylated molecule. PEGylation is one of several technologies that have been applied to extend the half-life of factor VIII; other recombinant factor VIII products use other technologies (such as fusion to protein conjugates or protein sequence modification).

Factor VIII is a procoagulant protein that is essential for blood clotting and maintenance of hemostasis. Hemophilia A is a hereditary disorder in which patients have a deficiency or defectiveness in endogenous factor VIII, resulting in a bleeding tendency. The severity of bleeding correlates with the degree of deficiency in factor VIII activity; in severe cases, the disease manifests as bleeds into joints, muscles, and soft tissues.

Patients with mild hemophilia A generally have 5-<40% of normal clotting factor activity, patients with moderate disease generally have 1-5% of normal activity, and those with severe disease have <1% of normal activity.

Administration of antihemophilic factor (recombinant), glycopegylated-exei to patients with hemophilia A results in increased plasma levels of factor VIII and temporarily corrects the coagulation defect in these patients. Administration of 1 IU/kg of antihemophilic factor (recombinant), glycopegylated-exei generally increases plasma factor VIII activity by 2 IU/dL. Treatment with antihemophilic factor (recombinant), glycopegylated-exei decreases the aPTT, which is prolonged in patients with hemophilia A.

Antihemophilic factor (recombinant), glycopegylated-exei (Esperoct(R)) is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells, and contains a truncated B domain, which is O-glycosylated. The recombinant factor VIII protein is purified using chromatographic steps, one of which is affinity chromatography, with the use of a monoclonal antibody to selectively isolate the recombinant factor VIII from the cell culture medium. The purification process includes two viral clearance steps, namely detergent treatment for inactivation of enveloped viruses, and 20-nm filtration for removal of enveloped and non-enveloped viruses.

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-IU/kg dose of antihemophilic factor (recombinant), glycopegylated-exei in patients with severe hemophilia A, the terminal half-life was 21.7 hours in adults, 17.4 hours in pediatric patients 12-<18 years of age, 13.8 hours in those 6-<12 years of age, and 14.7 hours in those 1-<6 years of age. Incremental recovery of factor VIII in these respective age groups was 2.53, 2.45, 1.67, and 1.82 IU/dL per IU/kg. There was a trend of increasing AUC and incremental recovery and decreasing clearance with age.

Compared to adult patients with a body mass index (BMI) <25 kg/m2, the following differences in pharmacokinetic parameters were observed in patients who were overweight (BMI 25-<30 kg/m2) and obese (BMI 30-<35 kg/m2): incremental recovery was increased by approximately 17% and 41%, AUC was increased by approximately 10% and 27%, and clearance was decreased by approximately 8% and 23%, respectively. The time to 5% factor VIII activity (mild hemophilia range) was 2.5 days in patients <12 years of age receiving 60 IU/kg twice weekly and 3.6, 3.6, and 4 days in those >=12 years of age receiving 50 IU/kg twice weekly, 50 IU/kg every 4 days, and 75 IU/kg every 7 days, respectively.

USES: This medication is used to control and prevent bleeding episodes in people with low levels of factor VIII (hemophilia A). It is also used in these patients before surgery to prevent bleeding. People with low factor VIII levels are at risk for bleeding longer after an injury/surgery and for bleeding inside the body (especially into the joints and muscles).

This product contains a man-made form of factor VIII, also called antihemophilic factor. This product is used to temporarily replace the missing factor VIII, a protein (clotting factor) that is normally in the blood, so that the blood can clot and the bleeding can stop. This medication should not be used to treat von Willebrand disease.

Generic name: antihemophilic factor (FVIII) rec, B-dom truncated peg-exei
Pronunciation: (AN-tye-HEE-moe-FIL-ik FAK-tor, ree-KOM-bi-nant)
Drug class: Antihemophilic Products
Therapeutic class: Hematological Agents

The following indications are listed for Esperoct:

• 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.