FDA OKs Treatment for Hemophilia A or B with Inhibitors

April 3, 2020

Coagulation factor VIIa (recombinant)-jncw (Sevenfact, LBF) contains an active ingredient from a genetically engineered animal.

Officials with the FDA have approved another option 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, according to a press release.

Coagulation factor VIIa (recombinant)-jncw (Sevenfact, LBF) 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, according to the FDA. The active ingredient is a recombinant analog of human FVIII, which is expressed in the mammary gland of genetically engineered rabbits and secreted into the rabbits’ milk, where it is converted into activated FVII.

“Based on 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,” Steven M. Solomon, DVM, MPH, director of the FDA’s Center for Veterinary Medicine. “The FDA has also determined under the National Environmental Policy that approval of the application will have no significant impact on the environment.”

The recombinant DNA construct in the genetically engineered rabbits used for the production of coagulation factor VIIa (recombinant)-jncw was approved by the FDA’s Center for Veterinary Medicine.

A clinical study including 27 patients with hemophilia A or B with inhibitors and the treatment of 465 mild or moderate, and 3 severe bleeding episodes, evaluated the safety and efficacy of coagulation factor VIIa (recombinant)-jncw. The efficacy of the treatment was evaluated 12 hours after the initial dose was given.

According to the results, the proportion of mild or moderate bleeding episodes treated successfully both with the lower dose of 75 mcg/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%. Additionally, 3 severe bleeding episodes were treated successfully with a higher dose.

In another study, the safety and pharmacokinetics of coagulation factor VIIa (recombinant)-jncw was evaluated with 3 escalating doses in 15 patients. Based on these results, the 2 doses (75 mcg/kg and 225 mcg/kg) were selected for evaluation in the efficacy study. The most common adverse effects associated with coagulation factor VIIa (recombinant)-jncw were headache, dizziness, infusion site discomfort, infusion-related reaction, infusion site hematoma, and fever.

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, according to the FDA. Hypersensitivity reactions, including anaphylaxis, may be possible. If experiencing symptoms of a thrombotic event or hypersensitivity reaction, patients should discontinue the therapy and seek appropriate medical interventions.

References:

1. FDA Approves Additional Treatment for Adults and Adolescents with Hemophilia A or B and Inhibitors [news release]. FDA’s website. https://www.fda.gov/news-events/press-announcements/fda-approves-additional-treatment-adults-and-adolescents-hemophilia-or-b-and-inhibitors. Accessed April 3, 2020.