General Information

SEVENFACT is a recombinant analog of human Factor VIIa, a vitamin K-dependent coagulation factor.

SEVENFACT is specifically indicated for the treatment and control of bleeding episodes occurring in adults and adolescents (12 years of age and older) with hemophilia A or B with inhibitors.

SEVENFACT is supplied as a powder for solution for intravenous administration. The Dose and duration of treatment depend on the location and severity of the bleeding, need for urgent hemostasis, frequency of administration, and known patient responsiveness to FVIIa-containing bypassing agents during prior bleeding events. Treatment with SEVENFACT should be initiated as soon as a bleeding event occurs.

The dose, frequency, and duration of SEVENFACT therapy should be based on the patient’s clinical response and hemostasis evaluation.

The use of laboratory assessment(s) of coagulation (PT/INR, aPTT, FVII:C) does not necessarily correlate with or predict the hemostatic effectiveness of SEVENFACT.

Maximum tolerated doses have not been determined for SEVENFACT, and cumulative daily doses greater than 900 mcg/kg, which may be associated with greater risk of thromboembolic complications, have not been studied.

Dose adjustment may be required if the patient has received other procoagulant therapies prior to treatment with SEVENFACT.

Based on the clinical trial program for SEVENFACT, the recommended initial dose should be adjusted based on the following criteria:

MILD TO MODERATE BLEEDING: 75 mcg/kg repeated every three hours until hemostasis is achieved OR Initial dose of 225 mcg/kg. If support healing and prevent recurrent hemorrhage after hemostasis to maintain hemostasis is not achieved within 9 hours, additional 75 mcg/kg doses may be administered every 3 hours as needed to achieve hemostasis. DURATION: continue therapy to support healing and prevent recurrent hemorrhage after hemostasis to maintain the hemostatic plug. The site and severity of bleeding should determine therapy duration.

SEVERE BLEEDING: 225 mcg/kg initially, followed if necessary 6 hours later with 75 mcg/kg every 2 hours until hemostasis is achieved. Continue therapy to support healing and prevent recurrent hemorrhage. The site and severity of bleeding and the use of other procoagulant therapies should determine therapy duration.

Mechanism of Action

The active ingredient in SEVENFACT is a recombinant analog of human Factor VIIa, a vitamin K-dependent coagulation factor. In the presence of both calcium and phospholipids, Factor VIIa in a complex with tissue factor (TF) activates Factor X to Factor Xa, directly bypassing the reactions that require Factor VIII or Factor IX. Activation of Factor X to Factor Xa initiates the common pathway of the coagulation cascade in which prothrombin is activated to thrombin, which then converts fibrinogen to fibrin to form a hemostatic plug, thereby achieving clot formation at the site of hemorrhage (hemostasis). This process may also occur in the absence of TF on the surface of activated platelets.

Side Effects

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

headache

dizziness

infusion-site discomfort

infusion-site hematoma

infusion-related reaction

fever

The SEVENFACT drug label comes with the following Black Box Warning of the potential for thrombosis. Serious arterial and venous thrombotic events may occur following administration of SEVENFACT. Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive SEVENFACT. Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.

Clinical Trial Results

The FDA approval of SEVENFACT was based on PERSEPT 1, a randomized, multicenter, open-label, two initial dose regimens, cross-over trial design trial. The trial evaluated 468 mild, moderate, and severe bleeding episodes in 27 adolescent and adult hemophilia A and B patients with inhibitors. Both initial dose regimens met the primary endpoint of bleed control by 12 hours: 91% of mild or moderate bleeding episodes treated with an initial 225 mcg/kg dose achieved hemostatic efficacy at 12 hours; the median time to hemostatic response was 3 hours, corresponding to 1 dose of SEVENFACT. The median time to hemostatic response for bleeding episodes treated with an initial 75 mcg/kg dose was 6 hours (median of 2 doses SEVENFACT), with 82% of bleeding episodes achieving hemostatic efficacy at 12 hours. By 24 hours, hemostatic efficacy was retained in 97.6% of bleeding episodes treated with the 75 mcg/kg dose regimen, and 99.5% of bleeding episodes treated with the 225 mcg/kg dose regimen, without requiring any alternative therapy.