Sevenfact for Hemophilia

Last updated Oct. 21, 2022, by Teresa Carvalho, MS

Fact-checked by Joana Carvalho, PhD


What is Sevenfact for Hemophilia?

Sevenfact (coagulation factor VIIa [recombinant]-jncw; eptacog beta) is an injectable medication used to treat and control spontaneous bleeding episodes in people with hemophilia A or hemophilia B with inhibitors.

It was developed by the Laboratoire Francais du Fractionnement et des Biotechnologies (LFB). HEMA Biologics holds Sevenfact’s marketing rights in the U.S. and Canada.

How does Sevenfact work?

In people with hemophilia, blood does not clot efficiently. This is either because their bodies cannot produce enough of certain clotting factors — specialized proteins involved in blood clotting — or, as is the case in acquired hemophilia, it mistakenly attacks its own clotting factors.

Hemophilia A patients have little or no clotting factor VIII (FVIII), while hemophilia B patients lack clotting factor IX (FIX).

Sevenfact is a type of bypassing agent that allows the body to bypass, or overcome, the need for standard clotting factor treatment. Its active ingredient is an artificial activated form of factor VII (FVII). This compound is isolated from the milk of genetically engineered rabbits and is then converted into its activated form through rPro technology.

It’s specifically intended for hemophilia A and B patients who develop inhibitors against clotting factor concentrates commonly used to prevent bleeds. Inhibitors are neutralizing antibodies that perceive the clotting factor as a foreign threat, lowering the effectiveness of standard replacement therapies.

Who can take Sevenfact?

Sevenfact was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for treating and controlling bleeding episodes in adults and adolescents, ages 12 and older, with hemophilia A or B with inhibitors. It was approved for the same indication in Mexico in June 2022.

It was also approved for the same indication in Europe, where it is being marketed under the brand name Cevenfacta.

Who should not take Sevenfact?

Sevenfact should not be used by people with a known allergy to rabbits or rabbit proteins, or those with a hypersensitivity to the treatment or any of its components.

The therapy is not indicated for treating congenital factor VII deficiency.

How is Sevenfact administered?

Sevenfact should be administered by intravenous (into-the-vein) infusion. For mild or moderate bleeds, patients are recommended to take Sevenfact at:

  • 75 micrograms per kilogram of body weight (mcg/kg) repeated every three hours until bleeding is controlled.

or

  • an initial dose of 225 mcg/kg; if bleeding is not controlled within the next nine hours, patients are recommended to take additional 75 mcg/kg doses every three hours as needed until bleeding is controlled.

For severe bleeds, patients are recommended to take Sevenfact at 225 mcg/kg, followed by additional 75 mcg/kg doses six hours later, if needed. Additional doses should be given every two hours.

Sevenfact is supplied as a white to off-white dry powder in single-use vials containing 1 or 5 mg of coagulation factor VIIa (recombinant)-jncw that should be reconstituted (diluted) with sterile water, supplied in single-dose prefilled glass syringes, as follows:

  • 1 mg (1,000 mcg) plus 1.1 mL sterile water in pre-filled syringe
  • 5 mg (5,000 mcg) plus 5.2 mL sterile water in pre-filled syringe

After reconstitution, each mL contains 1 mg of coagulation factor VIIa (recombinant)-jncw.

Prior to reconstitution, the medication should be stored, protected from light, at room temperature or in the fridge. It should not be frozen.

Sevenfact should be infused within four hours of being reconstituted. Each infusion usually takes two minutes or less and requires special training. Patients should not self-administer Sevenfact unless they have been trained by an experienced healthcare provider.

Sevenfact in clinical trials

Sevenfact’s approvals were supported by data from a series of Phase 3 trials that were all part of the PERSEPT clinical trial program.

PERSEPT 1 trial

The Phase 3 PERSEPT 1 trial (NCT02020369) assessed the safety and effectiveness of Sevenfact in controlling bleeds in 27 adults or adolescents with hemophilia A or B with inhibitors. The medication was given at a dose of 75 or 225 mcg/kg. During the study, Sevenfact was used to control 468 bleeding episodes, 465 of which were mild to moderate in severity.

Trial results showed that the lower dose of Sevenfact was able to control 84.9% of mild to moderate bleeds within 12 hours. The higher dosage had a greater success rate, at 93.2%. Three patients had severe bleeding episodes during the trial, which the higher dose successfully managed. Patients tolerated both doses well, causing no immune or adverse blood clotting responses.

PERSEPT 2 trial

An open-label Phase 3 trial called PERSEPT 2 (NCT02448680) evaluated Sevenfact’s safety and effectiveness in 25 boys, ages 1–11, with hemophilia A or B and inhibitors. Twelve boys were randomly assigned to receive an initial dose of 75 mcg/kg, and 13 were given a 225 mcg/kg dose. Patients switched between these dosing regimens every three months. The trial’s main goal was to successfully control mild or moderate bleeds within 12 hours of an infusion.

The study revealed Sevenfact was safe and effective at stopping bleeds either in the lower and higher dose groups, at 12 hours (65.4% vs. 60.3%) and 24 hours (97.4% vs. 98%).

PERSEPT 3 trial

The Phase 3 PERSEPT 3 trial (NCT02548143) assessed the safety and effectiveness of Sevenfact at treating bleeding episodes in boys and men with hemophilia A or B with inhibitors, who undergoing surgery or other invasive procedures.

The study found the therapy was safe and 100% effective at managing bleeds during and after minor surgeries, such as tooth extractions. In contrast, the treatment’s effectiveness at treating bleeds decreased with major surgeries, with positive results seen in 66.7% of the cases.

Ongoing trials

The American Thrombosis and Hemostasis Network is sponsoring a U.S.-based Phase 4 trial (NCT04647227) to evaluate Sevenfact in adolescents and adults with hemophilia A or B with inhibitors, including those on long-term prophylactic treatment with Hemlibra (emicizumab). The trial is expected to enroll up to 55 participants, ages 12 and older. The estimated completion date is June 2025.

Common side effects of Sevenfact

The most common side effects that have been associated with Sevenfact include:

  • headache
  • dizziness
  • injection site reactions, such as discomfort and hematoma
  • fever

Blood clotting

The therapy’s label contains a boxed warning stating that serious blood clotting events may occur in patients taking Sevenfact.

There is an increased risk of serious blood clotting issues if Sevenfact is used along with activated prothrombin complex concentrates by people with a history of congenital or acquired hemophilia. People with a history of blood clotting diseases or those who have conditions that affect blood flow and the blood vessels in the brain are also at an increased risk of such events while taking Sevenfact.

These risks should be assessed and patients closely monitored for any signs of blood clotting.

Allergic reactions

Because Sevenfact is generated in rabbits, patients with an allergy to rabbits should not use it. Patients with hypersensitivity (allergy) to any Sevenfact ingredient should also not take it. In case of severe allergic reactions (anaphylaxis), treatment should be stopped and patients should seek immediate medical attention.

Patients with a known allergy to casein, a protein found in milk, may be at higher risk of  hypersensitivity reactions with Sevenfact.

Development of inhibitors

Inhibitors may develop in patients treated with Sevenfact. When this occurs, treatment may not work as intended and bleeding control may not be achieved. Healthcare providers should perform blood tests regularly to monitor the presence of these neutralizing antibodies.

Use in pregnancy and breastfeeding

It’s currently not known if Sevenfact can affect the developing fetus or pass to breast milk. Patients who plan to become pregnant or breastfeed should talk with their healthcare professional and only continue treatment during these periods if the potential benefit justifies the potential risks to the fetus or infant.

 


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