General Information

Esperoct [antihemophilic factor (recombinant), glycopegylated-exei] is an extended half-life factor VIII molecule for replacement therapy in people with hemophilia A, which provides a 1.6-fold half-life prolongation in adults/adolescents and a 1.9-fold half-life prolongation in children, compared to standard half-life factor VIII products.

Esperoct is specifically indicated for use in adults and children with hemophilia A for: • On-demand treatment and control of bleeding episodes • Perioperative management of bleeding • Routine prophylaxis to reduce the frequency of bleeding episodes.

Espercot is supplied as a solution for intravenous infusion after reconstitution only. The recommended dose is as follows:

On-demand treatment/control of bleeding episodes: In adolescents / adults, 40 IU/kg body weight for minor/moderate bleeds and 50 IU/kg body weight for major bleeds; children (<12 years), 65 IU/kg body weight for minor/moderate/major bleeds.

Perioperative management: For minor/major surgery: In adolescents / adults: pre-operative dose of 50 IU/kg body weight; in children (<12 years), pre-operative dose of 65 IU/kg body weight. Frequency of administration is determined by the treating physician.

Routine prophylaxis: In adolescents/adults, 50 IU/kg every 4 days; in children (<12 years), 65 IU/kg twice weekly. A regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.

Esperoct also may be dosed to achieve a specific target Factor VIII activity level, depending on the severity of hemophilia, for on-demand treatment/control of bleeding episodes or perioperative management. To achieve a specific target Factor VIII activity level, use the following formula: Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL).

Clinical Results

FDA Approval

The FDA approval of Esperoct was based on the PATHFINDER program, five prospective, multi-center clinical trials in 270 previously treated patients (202 adults/adolescents and 68 children) with severe hemophilia A (<1% endogenous FVIII activity) and no history of inhibitors. Total exposure to Esperoct was 80,425 exposure days corresponding to 889 patient years of treatment. Esperoctwas shown to provide effective routine prophylaxis in people with severe hemophilia A through a fixed dosing regimen of one injection every 4 days in adults and adolescents or every 3-4 days (twice-weekly) in children.Esperoct provided effective prophylaxis and maintained a low median ABR of 1.18 when dosed at 50 IU/kg every 4 days in adults and adolescents. Esperoct was also found to be efficacious in treatment and control of bleeding episodes and perioperative management.

Mechanism of Action

Esperoct [antihemophilic factor (recombinant) is a glycopegylated form of recombinant anti-hemophilic factor, temporarily replaces the missing coagulation Factor VIII needed for effective hemostasis in congenital hemophilia A patients. The Factor VIII in Esperoct is conjugated to a 40-kDa polyethylene glycol molecule which increases the half-life and decreases the clearance compared to the non-pegylated molecule.