Kogenate FS (octocog alfa) for hemophilia

Last updated May 30, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is Kogenate FS for hemophilia?

Kogenate (octocog alfa) was an approved treatment used to prevent bleeding episodes, including those occurring during surgery, in people with hemophilia A. It was discontinued in 2022.

The medication was developed and marketed by Bayer. The company stopped its production in 2022, noting a “shift” from the use of standard half-life treatments like Kogenate to extended half-life products, which are designed to last longer in the bloodstream.

Before being discontinued, the therapy was being marketed in a new formulation, called Kogenate FS, which shortened its into-the-vein (intravenous) administration time due to its higher concentration.

Therapy snapshot

How does Kogenate FS work?

Hemophilia A is a bleeding disorder caused by mutations in the F8 gene that impairs the production or function of a blood-clotting protein called factor VIII (FVIII).

Kogenate FS contained octocog alfa, a man-made, or recombinant, version of FVIII that’s designed to temporarily replace the one that’s missing in the blood of hemophilia A patients, thereby helping to prevent and control bleeds.

Octocog alfa was produced from baby hamster kidney cells that were genetically modified to contain a copy of the human F8 gene, and thus to produce the FVIII protein. The protein is then harvested and purified for human use.

Octocog alfa is the same active ingredient of Kovaltry, an approved hemophilia A treatment also developed and marketed by Bayer, that is manufactured in a different way.

Who could take Kogenate FS?

Kogenate was first approved by the U.S. Food and Drug Administration in February 1993 for the control and prevention of bleeds, including occurring around the time of surgery, in hemophilia A patients.

In June 2000, a new formulation called Kogenate FS was approved. In this version, an inactive stabilizing ingredient called albumin was eliminated. The therapy was instead formulated in sucrose using a new purification process. The new formulation was supplied at a higher concentration, thereby reducing the medication’s infusion time.

In October 2008, Kogenate FS was approved as a routine prophylactic, or preventive, treatment to reduce the risk of bleeding episodes and the risk of joint damage in children with hemophilia A without pre-existing joint damage. The therapy was then approved as a prophylactic treatment for adults in May 2014.

Who should not take Kogenate FS?

Kogenate FS contained trace amounts of hamster and mouse proteins and thus was contraindicated, or not recommended, for patients with a history of allergic reactions, including severe and potentially life-threatening reactions, to mouse or hamster proteins.

It was also not recommended for people with a history of reactions to any of the medication’s inactive ingredients, such as sucrose, glycine, histidine, sodium, calcium chloride, polysorbate 80, imidazole, tri-n-butyl phosphate, or copper.

In addition, the therapy was not indicated for von Willebrand disease, another inherited bleeding disorder.

How was Kogenate FS administered in hemophilia?

Kogenate FS was given as an intravenous injection. The therapy was available as a powder in single-use vials containing 250, 500, 1,000, 2,000, and 3,000 international units (IU) of FVIII.

The therapy was designed to be reconstituted, or diluted, before being administered with the components provided with its package.

After reconstitution, Kogenate FS was to be stored at room temperature before being administered within a period of three hours. Administration usually took between one and 15 minutes, and the rate of administration was adapted to each patient’s response. Patients might be able to self-administer the treatment after receiving proper training from a healthcare provider or hemophilia treatment center.

Treatment dosage and frequency were calculated based on the degree of FVIII deficiency, and the location and severity of the bleeding episode, or in anticipation of the type of surgery a patient required, and titrated based on each person’s clinical response.

For routine prophylaxis in adults, a dosage of 25 IU per kilogram of body weight (IU/kg) injected three times per week was recommended. Children were prescribed the same dose, but given every other day.

For the control and treatment of active bleeds, patients were given:

• a dose of 10 to 20 IU/kg, to be taken until the bleed was resolved (with a dose repetition if needed), in the case of minor bleeds (e.g. minor muscle or oral bleeds).
• a dose of 15 to 30 IU/kg, to be administered every 12-24 hours until the bleed was resolved, in the case of moderate bleeds (e.g. muscle and joint bleeds, or those resulting from known trauma).
• an initial dose of 40 to 50 IU/kg, followed by a dose of 20 to 25 IU/kg given every 8-12 hours until the bleed was resolved, in the case of major bleeds (e.g. bleeding into the brain or gastrointestinal tract, fractures, and head trauma).

For minor surgical procedures (e.g. tooth extraction), a dose of 15 to 30 IU/kg was to be given every 12-24 hours until bleeding was resolved. For major surgical procedures (e.g. joint replacement surgery or surgery involving the brain), a dose of 50 IU/kg was to be given before surgery and every 6-12 hours to maintain FVIII levels in the desired range until healing was complete.

Kogenate FS in hemophilia clinical trials

Findings from a number of open-label studies backed the approval of Kogenate FS.

Across these studies, 73 previously treated patients with severe hemophilia A, ages 12-59, received Kogenate FS as an on-demand or prophylactic treatment for up to 54 months (4.5 years). Over a total of 5,684 bleeding episodes, 92.7% were controlled with one or two infusions. Among 30 patients who received Kogenate FS around the time of surgery (41 procedures), the surgeon rated bleed control as “excellent” or “good” in all cases.

Another clinical study evaluated Kogenate FS in 37 previously untreated and 24 minimally treated patients with severe hemophilia A. Over about a three-year period, a total of 1,047 treated bleeding episodes occurred, with the majority being controlled with one or two infusions of Kogenate FS. Twenty-two of those patients were given Kogenate FS during surgery, with bleed control again deemed to be “excellent” or “good” in all cases.

Joint Outcome Study

The Joint Outcome Study (NCT00207597) enrolled 65 boys with hemophilia A, 2.5 years old and younger, who were randomly assigned to received Kogenate or Kogenate FS, either for routine prophylaxis (25 IU every other day) or as an enhanced episodic (on-demand) therapy, given only at the time of a clinically recognized joint bleed.

By 6 years of age, 93% of the boys on preventive therapy and 55% on episodic treatment were found to have normal joint structure on MRI scans, reflecting a significant protective effect of prophylactic Kogenate on joint health. Mean annual numbers of joint and total bleeds were significantly higher in the episodic therapy group. These findings supported Kogenate’s approval as a preventive therapy for children.

SPINART trial

Kogenate FS’s approval for routine prophylaxis in adults was based on data from the Phase 3 SPINART trial (NCT00623480). The randomized, open-label study assessed the safety and efficacy of the therapy in 84 male patients, ages 12-50, who were randomly assigned to receive on-demand or prophylactic treatment with Kogenate FS for at least one year.

Results showed that after a median of 1.7 years of treatment, patients given Kogenate FS as a prophylactic treatment had a significantly lower median number of bleeding episodes per year than those given on-demand treatment, with a 93% relative reduction in bleed frequency. The safety profile of prophylactic Kogenate FS was similar to that of on-demand treatment.

Common side effects of Kogenate FS

Common side effects associated with Kogenate FS that were reported in clinical trials included:

• development of neutralizing antibodies (inhibitors) against FVIII in previously untreated or minimally treated patients
• infusion site reactions (e.g. inflammation and pain)
• skin hypersensitivity reactions (e.g. rash and itching)
• infections associated with the placement of devices to access veins.

Allergic reactions

Allergic reactions, including a potentially life-threatening reaction known as anaphylaxis, have been reported in patients treated with Kogenate FS. Symptoms of an allergic reaction might include rash, itching, tightness of the chest or throat, difficulty breathing, light-headedness or dizziness, nausea, and a decrease in blood pressure.

Because Kogenate FS contained small amounts of mouse and hamster proteins, it was possible that patients given the therapy developed allergic reactions to these animal proteins.

If such reactions occurred, treatment was to be stopped immediately and emergency treatment sought.

Development of inhibitors

Development of neutralizing antibodies, or inhibitors, have been reported following treatment with Kogenate FS, particularly in previously untreated patients. These inhibitors had the potential to prevent the treatment from working as intended.

Patients were to be regularly monitored for the possible development of inhibitors. Tests to check for the presence of inhibitors were to be performed if bleeding did not stop after treatment, or if the patient failed to reach expected FVIII activity levels.

Use in pregnancy and breastfeeding

It’s unknown if Kogenate FS was safe to use during pregnancy or breastfeeding. No animal reproduction studies have been conducted with Kogenate FS, so no data are available about whether the therapy could be harmful to a developing fetus or to female reproduction capacity. According to its prescribing information, the medication should only be administered to pregnant women if clearly needed.

It’s also not known if Kogenate FS could pass into breastmilk when administered to nursing women.

Patients who were pregnant or planning to become pregnant or breastfeed were strongly advised to discussed the potential benefits and risks with their healthcare team.

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