Contact Information

Contact: Bayer

Website: https://www.bayer.com/en/

Currently Enrolling Trials

General Information

Kogenate FS is a new formulation of recombinant factor VIII formulated with sucrose, as opposed to human plasma protein (albumin). Kogenate FS has a higher concentration and smaller fluid volume, which reduces the intravenous infusion time, thus allowing individuals to infuse more rapidly. It was designed to temporarily replace the missing clotting factor VIII that is needed for effective hemostasis.

Kogenate FS is specifically indicated for:

The control and prevention of bleeding episodes in adults and children (zero to 16 years) with hemophilia A;
Surgical prophylaxis in adults and children with hemophilia A; and
Routine prophylactic treatment to reduce the frequency of bleeding episodes and the risk of joint damage in children with no pre-existing joint damage.

Mechanism of Action

Kogenate FS temporarily replace the missing clotting factor VIII that is needed for effective hemostasis.

Side Effects

Adverse events associated with the use of Kogenate FS may include, but are not limited to, the following:

Rash
Pruritus
Infusion site reactions
Inflammation
Pain
Central venous access device (CVAD) line-associated infections in patients requiring a CVAD for intravenous administration

Dosing/Administration

Kogenate FS is supplied as a lyophilized powder (as either 250, 500, 1000, and 2000 International Units) for reconstitution to be administered via intravenous infusion. The recommended dose depends on the severity of the factor VIII deficiency, the location and extent of bleeding and the patient’s clinical condition. The appropriate dose can be estimated according to the following calculations:

Dosage (units) = body weight (kg) x desired factor VIII rise (IU/dL or % or normal) x 0.5 (IU/kg per IU/dL)

-OR-

IU/dL (or percentage normal) =Total Dose (IU)/body weight (kg) x 2 [IU/dL]/[IU/kg]

Control and Prevention of Bleeding Episodes

Minor bleeding: Factor VIII level required (IU/dL or percentage of normal) is 20 to 40 IU per kg; dosage and frequency necessary to maintain the therapeutic plasma level is 10 to 20 IU per kg. Repeat dose if there is evidence of further bleeding.

Moderate bleeding: Factor VIII level required (IU/dL or percentage of normal) is 30 to 60 IU per kg; dosage and frequency necessary to maintain the therapeutic plasma level is 15 to 30 IU per kg. Repeat dose every 12 to 24 hours until bleeding is resolved.

Major bleeding: Factor VIII level required (IU/dL or percentage of normal) is 80 to 100 IU per kg; dosage and frequency necessary to maintain the therapeutic plasma level: initial dose 40 to 50 IU per kg. Repeat dose 20 to 25 IU per kg every eight to 12 hours until bleeding is resolved.

Peri-operative Management

Minor Surgery: Factor VIII level required (IU/dL or percentage of normal) is 30 to 60 IU per kg. Dosage and frequency necessary to maintain the therapeutic plasma level: 15 to 30 IU per kg Repeat dose every 12 to 24 hours until bleeding is resolved.

Major Surgery: Factor VIII level required (IU/dL or percentage of normal) is 100 IU per kg. Dosage and frequency necessary to maintain the therapeutic plasma level: pre-operative dose 50 IU per kg. Verify 100 percent activity prior to surgery. Repeat as necessary after six to 12 hours initially and for 10 to 14 days until healing is complete.

Routine Prophylaxis in Children with No Pre-existing Joint Damage

The recommended dose for routine prophylaxis is 25 IU/kg of body weight every other day.

Clinical Trial Results

The FDA approval of Kogenate FS was based on the following studies:

Previously Treated Patients

A series of open label studies in Europe and North America enrolled a total of 73 subjects (ages 12 to 59) with severe hemophilia A who had been previously treated with other recombinant or plasma-derived AHF products. The subjects were treated up to 54 months with Kogenate FS. A total of 5,684 bleeding episodes were treated during the study. The subjects could be treated on demand or on prophylaxis. Regularly scheduled prophylaxis treatment represented 76 percent of all infusions (treatment regimens of two to three infusions per week). Percentage of bleeds treated with one or two infusions of Kogenate FS: one infusion: 79.7 percent; two infusions: 13.0 percent. Mean Kogenate FS dose per treatment infusion (in Europe and North America, respectively): approximately 32.5 and 29.6 IU/kg per treatment infusion. Hemostasis was rated by the treating physician as satisfactory (excellent or good) in all cases.

Previously Untreated and Minimally Treated Patients (PUPs and MTPs)

There were 37 PUPs and 24 MTPs (defined as having equal to or less than four exposure days) treated with a total of 9,419 infusions of Kogenate FS for a follow up duration up to 3.1 years. A total of 1,047 bleeding episodes were treated. The median number of exposure days to Kogenate FS was 115 days. Percentage of bleeds treated with one or two Infusions of Kogenate FS: one infusion 73.1 percent; two infusions 15.0 percent. Hemostasis was rated as satisfactory (excellent or good) in all cases by the treating physician.

Pediatric Prophylaxis and Joint Damage Risk Reduction

This was a long-term study of Kogenate as a prophylactic treatment of hemophilia in pediatric subjects. This five-year, randomized trial was designed to compare the prophylactic with episodic on-demand use of Kogenate for treatment in children with hemophilia A. The trial enrolled 65 boys between the ages of six months and 30 months. The subjects were randomized to receive either a prophylaxis regimen consisting of 25 IU/kg rFVIII every other day or enhanced episodic treatment consisting of at least three doses of rFVIII totaling a minimum of 80 IU/kg at the time of a joint bleed. The boys were followed for six years and subsequently assessed for bone or cartilage damage, joint function, number of joint hemorrhages, and amount of product consumed. The subjects in the prophylaxis group had significantly fewer joint hemorrhages per year and overall number of bleeds per year compared to the subjects on episodic treatment (mean joint bleeds 0.63 vs. 4.89, respectively; mean total bleeds 3.27 vs. 17.69, respectively; P less than 0.001 for both comparisons. When evaluated by MRI at the end of six years, 9 percent% of the subjects in the prophylaxis group had joints that appeared normal compared to 55 percent in the episodic group (P=0.002). The correlation of hemarthroses with joint scores as measured with MRI was r=0.26 (P less than 0.001). Finally, joint or cartilage damage was confirmed in 7 percent of the subjects in the prophylaxis group compared to 45 percent in the episodic group (P=0.002).