Factor VII Treatment Eptacog Beta Now Under Review in Europe

The European Medicines Agency (EMA) has agreed to review an application by Laboratoire Francais du Fractionnement et des Biotechnologies, a French biopharmaceutical known as LFB, requesting the approval of eptacog beta for the treatment of bleeding episodes in patients with hemophilia A or B with inhibitors.

A decision is expected by mid-2022, LFB announced in a press release.

Should the European Commission approve the therapy, health authorities in each European Union member state will decide whether to add eptacog beta to their respective public health programs. Doing so would allow patients in those countries to access the treatment at low or no cost.

The announcement came less than a year after the therapy was approved in the U.S., under the brand name Sevenfact, for the treatment and control of bleeds in adults and adolescents, ages 12 and older, with hemophilia A or hemophilia B with inhibitors.

People with inherited hemophilia have a deficiency in specific clotting factors — factor VIII (FVIII) in hemophilia A and factor IX (FIX) in hemophilia B — that impair their ability to make blood clots needed to prevent excessive bleeding.

Replacement therapy, a standard prophylactic, or preventive, treatment for both types of hemophilia, consists of the regular administration of the missing clotting factors to patients as a preventive measure to avoid spontaneous bleeds.

However, many patients develop inhibitors, or neutralizing antibodies, against these clotting factors, reducing the treatment’s effectiveness.

A bypassing agent, eptacog beta was designed to promote blood clotting specifically in hemophilia A or B patients who developed inhibitors to FVIII or FIX replacement therapies.

Its active ingredient, an artificial form of factor VII (FVII), is purified from the milk of genetically engineered rabbits, and subsequently converted into its activated form (FVIIa) through LFB’s proprietary rPro technology. The therapy is administered directly into a patient’s bloodstream.

The regulatory application was based on data from three completed, international, pivotal Phase 3 clinical trials: PERSEPT 1 (NCT02020369), PERSEPT 2 (NCT02448680), and PERSEPT 3 (NCT02548143).

These studies evaluated eptacog beta’s safety and efficacy at treating bleeding episodes in children and adults with hemophilia A or B with inhibitors. They also assessed the treatment’s ability to safely and effectively prevent bleeding episodes in those undergoing surgery or other invasive procedures.

Data from PERSEPT 1 showed that the two doses of eptacog beta evaluated — 75 and 225 micrograms per kilogram— were generally well-tolerated and effectively controlled most mild to moderate bleeding episodes in 27 patients with hemophilia A or B with inhibitors. The higher dose was associated with a higher success rate.

In parallel, LFB announced the publication of results from an exploratory preclinical study of the coagulation-induced activity of eptacog beta, when used alone or in combination with Hemlibra (emicizumab), an approved replacement therapy for hemophilia A.

The company-sponsored study assessed the coagulation-induced activity of the therapy, alone or in combination, when added to blood from hemophilia A patients with and without inhibitors. It was done by analyzing the levels of thrombin, a blood-clotting protein.

Data showed that the combination of several doses, including clinically relevant doses of both therapies resulted in a dose-dependent, significant increase in thrombin generation in blood with and without inhibitors.

Importantly, thrombin levels did not exceed those observed in blood from healthy people, suggesting that the combination treatment does not increase the risk of thrombotic complications in hemophilia patients. Thrombotic events are those related to the formation of blood clots that impair normal blood flow.

This supported the hypothesis that eptacog beta “may have a thrombotic safety profile similar to that of [NovoSeven], and might in turn avoid the thrombotic complications observed with the combination of aPCC [activated prothrombin complex concentrate] and [Hemlibra] in this patient population,” the researchers wrote.

Similar to eptacog beta, Novo Nordisk’s NovoSeven (eptacog alfa) is a bypassing agent that stimulates blood clotting by providing an artificial form of FVIIa to patients.

The team noted that these findings, along with the recommendation of the National Hemophilia Foundation’s Medical and Scientific Advisory Council, support the use of eptacog beta for treating bleeds in patients on prophylactic Hemlibra. They also highlight the therapy’s potential as a new bypassing agent to support this patient group.

The American Thrombosis and Hemostasis Network, in collaboration with LBS, plans to launch a U.S.-based Phase 4 clinical trial (NCT04647227) in the coming months to evaluate eptacog beta in up to 55 adolescents and adults with hemophilia A or B with inhibitors, including those on long-term prophylactic treatment with Hemlibra.