General Information

Eloctate is a long-acting fully-recombinant Factor VIII Fc fusion (rFVIIIFc) protein that temporarily replaces the missing Coagulation Factor VIII needed for effective hemostasis.

Eloctate is specifically indicated for use in adults and children with Hemophilia A (congenital Factor VIII deficiency) for the control and prevention of bleeding episodes, perioperative management (surgical prophylaxis) and routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

Eloctate is supplied as a lyophilized powder for reconstitution for intravenous injection. Dose and duration of treatment depend on the severity of the Factor VIII deficiency, the location and extent of bleeding, and the patient’s clinical condition. Careful monitoring of replacement therapy is necessary in cases of major surgery or life-threatening bleeding episodes. One unit per kilogram body weight will raise the Factor VIII level by 2% international units per deciliter [IU/dL]. Each vial of Eloctate is labeled with the amount of recombinant factor VIII in IU.<br>Dosing formula for bleeding episodes and perioperative management:<br>Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg)  OR Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)<br>Dosing for routine prophylaxis is:<br>50 IU/kg every 4 days; it may be adjusted based on patient response with dosing in the range of 25-65 IU/kg at 3-5 day intervals. More frequent or higher doses up to 80 IU/kg may be required in children less than 6 years of age.

Clinical Results

FDA Approval

The FDA approval of Eloctate was based on an open label phase III trial in 165 previously treated male subjects with severe hemophillia. The subjects received rFVIIIc in one of three arms: individualized prophylaxis, weekly prophylaxis and episodic (on-demand) treatment (Arms 1, 2 and 3, respectively). The primary endpoints were safety, pharmacokinetics and efficacy, measured by the annual number of bleeding episodes (spontaneous and traumatic) at 156 weeks. The median annualized bleeding rates (ABR), including spontaneous and traumatic bleeds, were 1.6 in the individualized prophylaxis arm, 3.6 in the weekly prophylaxis arm and 33.6 in the episodic treatment arm. In the individualized prophylaxis arm, the median dosing interval was 3.5 days. During the last three months on study, 30% of subjects in the individualized prophylaxis arm achieved a mean dosing interval of five days. Overall, 98% of bleeding episodes were controlled by one or two injections of rFVIIIFc. In addition, rFVIIIFc was assessed in the perioperative management of nine patients undergoing nine major surgical procedures. The treating physicians rated the hemostatic efficacy of rFVIIIFc as excellent or good in 100 percent of these surgeries. Recombinant FVIIIFc was generally well-tolerated. No inhibitors to rFVIIIFc were detected and no cases of anaphylaxis were reported.

Side Effects

Adverse effects associated with the use of Eloctate may include, but are not limited to, the following:

• arthralgia
• malaise

Mechanism of Action

Eloctate is a long-acting fully-recombinant Factor VIII Fc fusion (rFVIIIFc) protein that temporarily replaces the missing Coagulation Factor VIII needed for effective hemostasis. Eloctate contains the Fc region of human immunoglobulin G1 (IgG1), which binds to the neonatal Fc receptor (FcRn). FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by cycling them back into circulation and prolonging their plasma half-life.

Additional Information

For additional information regarding Eloctate or hemophilia A, please visit www.Eloctate.com