The U.S. Food and Drug Administration today approved Sevenfact [coagulation factor VIIa (recombinant)-jncw] 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 (neutralizing antibodies). Sevenfact contains an active ingredient expressed in genetically engineered rabbits.

“Today’s approval provides another treatment option for the control of bleeding episodes in adults and adolescents with hemophilia who have developed inhibitors,” said Dr. Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “In addition to being an important option for patients, Sevenfact is the first product for hemophilia treatment that contains an active ingredient obtained from rabbits genetically engineered to produce a protein necessary for blood coagulation. This approval is an example of our efforts to advance safe biotechnology innovations to support patient health.”

Hemophilia A or B is a congenital bleeding disorder caused by a dysfunction or deficiency of Coagulation Factor (F) VIII or IX, respectively. People with hemophilia may bleed for a longer time than others after injury or surgery. They may also have spontaneous bleeding in muscles, joints and organs, which may be life-threatening. Individuals with inhibitors may not respond to factor replacement therapy. According to the Centers for Disease Control and Prevention (CDC), there are an estimated 20,000 people living with hemophilia in the United States. Bleeding episodes in these individuals are managed by either on-demand treatment or prophylaxis using products containing FVIII or FIX. However, when inhibitors to FVIII or FIX develop in these individuals, treatment of bleeding episodes with FVIII or FIX products may no longer be effective. In these situations, the administration of products such as Sevenfact, which bypass the Factor VIII and Factor IX reactions, promotes clot formation and controls bleeding.

The active ingredient of Sevenfact is a recombinant analog of human FVII, which is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits’ milk. During purification and processing of the milk, FVII is converted into activated FVII (FVIIa).

The recombinant DNA (rDNA) construct in the genetically engineered rabbits used for the production of Sevenfact was approved by the FDA’s Center for Veterinary Medicine.

“Based on a comprehensive analysis of the scientific evidence, the FDA determined that the rDNA construct inserted in the rabbit’s genomic DNA is safe for the animal and for the people handling the rabbits, and is effective in causing Human Factor VII (hFVII) protein to be expressed in the rabbits’ milk,” said Steven M. Solomon, D.V.M., M.P.H., director of the FDA’s Center for Veterinary Medicine. “The FDA has also determined under the National Environmental Policy Act that approval of the application will have no significant impact on the environment.”

The safety and efficacy of Sevenfact were determined using data from a clinical study that evaluated 27 patients with hemophilia A or B with inhibitors, which included treatment of 465 mild or moderate, and three severe bleeding episodes. The study assessed the efficacy of treatment 12 hours after the initial dose was given. The proportion of mild or moderate bleeding episodes treated successfully both with the lower dose of 75mcg/kg and higher dose of 225 mcg/kg (requiring no further treatment for the bleeding episode, no administration of blood products and no increase in pain beyond 12 hours from initial dose) was approximately 86%. The study also included three severe bleeding episodes that were treated successfully with the higher dose.

Another study evaluated the safety and pharmacokinetics of three escalating doses of Sevenfact in 15 patients with severe hemophilia A or B with or without inhibitors. Results from this study were used to select the two doses, 75mcg/kg and 225 mcg/kg, that were evaluated in the study described above.

The most common side effects of Sevenfact were headache, dizziness, infusion site discomfort, infusion related reaction, infusion site hematoma and fever.

Sevenfact is contraindicated in patients with known allergy or hypersensitivity to rabbits or rabbit proteins.

Patients with hemophilia A or B with inhibitors who have other risk factors for blood clots (thrombosis) may be at increased risk of serious arterial and venous thrombotic events. Hypersensitivity reactions, including anaphylaxis, are possible. Should symptoms of a thrombotic event or hypersensitivity reaction occur, patients should discontinue Sevenfact and seek appropriate medical intervention.

The FDA granted approval of Sevenfact to Laboratoire Francais du Fractionnement et des Biotechnologies S.A.

Posted on the FDA website on 1 April 2020