Extended Half-Life (EHL) Products

The recommended treatment regimen for patients with severe hemophilia to prevent bleeding episodes is to replace the deficient clotting factor. However, currently available replacement clotting factors are limited by their relatively short half-lives and require intravenous injections up to three times a week to maintain protective levels. This can have a negative impact on patient compliance.

Recent research has led to the development of new factor products that are equally efficient with less frequent need for injections — once every week or two. The fewer injections are due to the medication’s increased half-life, which is the amount of time the body takes to reduce the clotting factor to half in the bloodstream. In other words, the structure of the protein factor molecules is altered so the body takes longer to clear them from the circulation, meaning that they work longer after being injected. These drugs are collectively called extended half-life, or EHL treatments.

The clotting factors with extended half-life have several advantages, including reduced injection frequency, increased treatment adherence, and improved clinical outcomes. Long-acting clotting factors also provide an opportunity for improved individualized treatment for hemophilia.

There are three ways of producing EHL products: Fc fusion, PEGylation, and albumin fusion.

Fc fusion

Biogen, in partnership with Swedish Orphan Biovitrum (Sobi), has been granted approval for two new EHL products in which a fragment of Fc, a protein found in immunoglobulin (antibodies), is fused to a recombinant clotting factor. This makes the treatment last for days or weeks instead of a few hours. The two approved EHL products synthesized in this way are Alprolix for hemophilia B and Eloctate for hemophilia A.


Pharma companies including Novo Nordisk, Baxter, and Bayer are using a technique called PEGylation, in which a compound called polyethylene glycol (PEG) is conjugated to clotting factors to extend their half-life. PEGylated products have already been approved in other therapeutic areas.

The U.S. Food and Drug Administration is expected to make a decision soon on Novo Nordisk’s glycoPEGylated EHL factor IX drug for hemophilia B, called Refixia (N9-GP). Another EHL PEGylated factor VIII drug for hemophilia A, called N8-GP (turoctocog alfa pegol), is being investigated in a series of clinical trials.

For hemophilia A, PEGylated factor VIII products are being developed by Baxter (BAX-855) and Bayer (Jivi).

Albumin fusion

The third approach to extend the half-life of clotting factors is fusion with recombinant albumin, which is a protein that occurs naturally in the blood. An albumin-fused factor IX (CSL654, also known as Idelvion) for hemophilia B by CSL Behring is being investigated in clinical studies; results have shown that fewer doses of albumin-fused factor IX are sufficient to treat hemophilia B.


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