Fc fusion for hemophilia

Last updated Jan. 23, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD

What is Fc fusion for hemophilia?

Fc fusion is one of the molecular technologies that has been used to create extended half-life replacement therapies for hemophilia.

A replacement therapy is a hemophilia treatment that contains a functional version of the clotting protein that’s missing or is defective in a person with hemophilia. Such therapies contain clotting proteins specific to the type of hemophilia the individual has — factor VIII (FVIII) in the case of hemophilia A and factor IX (FIX) for hemophilia B. By providing the missing protein, factor replacement therapies can help control and prevent bleeding episodes in people with hemophilia.

Naturally occurring versions of clotting factor proteins are not very stable in the bloodstream. Thus, traditional replacement therapies, which use versions of clotting factors that are essentially identical to the proteins normally produced in the body, need to be administered fairly frequently to maintain clotting factor levels high enough to prevent bleeds. With prophylactic, or preventive, treatment, most have to be administered several times per week.

Extended half-life or EHL therapies are a new type of replacement therapy in which clotting factors have been molecularly modified to be more stable in the blood. Because these modified clotting factors are more stable than those provided by conventional replacement therapies, they remain in circulation for longer periods of time and don’t need to be administered as often to achieve the same therapeutic effect.

Fc fusion is one of the technologies that can be used to make long-lasting versions of clotting factors. It has been used to create both an EHL factor IX and factor VIII replacement therapy for use in hemophilia patients.

How does Fc fusion work in hemophilia?

Antibodies are Y-shaped molecules made by the immune system that help fight off infections and other potential threats. Their tail region is called the Fc domain — short for “fragment crystallizable” domain — and allows them to interact with receptors at the surface of immune cells to trigger certain immune responses upon binding to a specific target.

In some antibodies, the Fc domain also enables them to interact with the neonatal Fc receptor, a protein receptor that helps prevent their degradation and redirects them back into circulation. This enables them to remain active in the bloodstream for longer periods of time.

Fc fusion technology basically works by attaching the Fc domain to a specific protein of interest — a clotting factor in the case of hemophilia — creating what is referred to as an Fc fusion protein.

Just as this domain normally helps prevent antibodies from being degraded, adding the Fc domain to clotting factor proteins also makes them more stable and long-lasting in the bloodstream. Fc fusion also is thought to slow the rate at which modified molecules are eliminated from the body through the kidneys due to their larger size.

Fc fusion in hemophilia therapies

Three EHL treatments that employ Fc fusion technology have been approved for hemophilia in the U.S.: Eloctate and Altuviiio for hemophilia A, and Alprolix for hemophilia B.

Eloctate

Eloctate (efmoroctocog alfa) is approved for on-demand and prophylactic treatment in adults and children with hemophilia A. As a preventive treatment, the starting dosing regimen is every four days for patients ages 6 and older, and twice weekly for children younger than 6. Given by an injection directly into the bloodstream, Eloctate is sold by Sanofi in the U.S., Canada, and several other countries; in Europe and other regions, it is marketed under the brand name Elocta by Sobi.

Altuviiio

Altuviiio (efanesoctocog alfa) also is an approved treatment, both for on-demand and prophylactic use in the U.S., for adults and children with hemophilia A. It’s given by an intravenous or into-the-vein injection, and when used for prophylaxis, the dosing schedule is one injection per week. Altuviiio is marketed by Sanofi in collaboration with Sobi.

Alprolix

Alprolix (eftrenonacog alfa) is widely approved to treat and prevent bleeds in adults and children with hemophilia B. It’s given by an intravenous injection, and the recommended starting dosing schedule for prophylaxis is one injection once weekly or every 10 days. Alprolix also is sold by Sanofi and Sobi.

Experimental Fc fusion therapies for hemophilia

Jiangsu Gensciences is developing an experimental EHL replacement therapy for hemophilia A called FRSW117. It contains a version of the FVIII protein that’s modified with Fc fusion, in addition to another technology called PEGylation. FRSW117, which is expected to be given once weekly to prevent bleeds in adults and adolescents, is being tested in clinical trials.

The company also is developing another EHL replacement therapy for hemophilia A, based on Fc fusion and called FRSW107. This therapy is expected to enable a twice weekly dosing frequency in adult and adolescent patients. FRSW107 is in Phase 3 testing in China.

In addition to hemophilia A, Jiangsu Gensciences is developing an EHL replacement therapy for hemophilia B that incorporates both Fc fusion and PEGylation. Called SS327, the therapy is expected to be given every 10 to 14 days; it’s now in the early stages of clinical testing.

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