Albumin fusion for hemophilia
Fact-checked by
What is albumin fusion for hemophilia?
Albumin fusion is a molecular technology that has been used to create replacement therapies for hemophilia with an extended half-life — treatments that are more long-lasting in the body and can therefore be administered less frequently.
Hemophilia is caused by mutations that impair the production or activity of clotting proteins that are essential to stop bleeds. In hemophilia A, this clotting protein is factor VIII (FVII); in hemophilia B, it’s factor IX (FIX). Factor replacement therapies are a cornerstone of hemophilia treatment and involve administering a functional version of the missing clotting protein to patients.
The first replacement therapies that were developed for hemophilia use forms of FVIII and FIX that are essentially identical to the naturally-occurring versions of the proteins. While these therapies can be highly effective for controlling and preventing bleeds, the clotting factors they provide are not very stable in the blood. As a result, standard factor replacement therapies have to be administered quite frequently — generally multiple times per week — to maintain clotting factor levels high enough to prevent bleeds.
Extended half-life therapies, or EHLs, are next-generation replacement therapies in which the clotting factors have been engineered to be more stable in the body. That allows them to be given less often than conventional replacement therapies. Albumin fusion is one of the technologies that’s been used to create these EHL treatments.
How does albumin fusion work in hemophilia?
Albumin, the most abundant protein found in plasma — the liquid portion of blood — is normally produced by the liver and rapidly released into the bloodstream. There, it acts as a molecular ferry, helping to transport hormones and other molecules through the bloodstream.
One of the reasons albumin is well-suited to transport other molecules in the body is that the protein is very stable in the bloodstream. In humans, albumin has an average plasma half-life of three weeks, meaning that it takes roughly three weeks for its total level to drop to half following production. That’s due in large part to its interaction with the neonatal Fc receptor, a protein receptor that normally works to prevent the degradation, and promote the recycling, of antibodies and albumin circulating in the blood.
In albumin fusion, as the term suggests, the albumin protein is attached, or fused, to another molecule, stabilizing it and helping extend the time it remains in circulation. In the context of hemophilia, albumin is attached to clotting factor proteins, slowing the rate at which these proteins are degraded in the blood.
This technology also has been used to develop treatments — though none are now in use — for other indications. One such therapy was albiglutide, which had been approved in the U.S. under the brand name Tanzeum to help manage blood sugar in people with type 2 diabetes. This treatment later was discontinued due to limited use. Another example was balugrastim, which was being developed under the name Egranli in Europe as a treatment to manage low immune cell counts in adults with cancer undergoing chemotherapy. Applications seeking the approval of balugrastim for this indication ended up being withdrawn in both the U.S. and Europe.
Albumin fusion in hemophilia therapies
The first clotting factor therapy employing albumin fusion to earn regulatory approval for hemophilia was Idelvion (albutrepenonacog alfa), a FIX replacement therapy that’s approved in the U.S. to prevent and manage bleeds in adults and children with hemophilia B.
Idelvion also is approved in the European Union, Japan, and elsewhere. The therapy, developed and marketed by CSL Behring, is administered via an intravenous or into-the-vein infusion. When used for prophylaxis, or as preventive treatment, Idelvion’s recommended starting dosing schedule is once weekly, but it may be given less frequently depending on the individual’s response.
Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Related articles
