Hemophilia B Research Update
Hemophilia B is a rare bleeding disorder that causes blood to clot more slowly than usual. If you have this condition, you may have prolonged bleeding or oozing after an injury or surgery. In severe cases, you may have prolonged bleeding after a minor or even no injury.
Hemophilia B is caused by genetic mutations in the F9 embarrassed. This gene gives your body instructions to produce factor IX. It is one of multiple clotting factors that help your blood clot. If you have hemophilia B, your body does not produce enough factor IX.
The first-line treatment is factor IX replacement therapy. Your doctor will give you high doses of factor IX concentrate to stop bleeding episodes. They may also prescribe factor IX prophylaxis, which involves taking regular doses of factor IX concentrate to help prevent bleeding.
You may find prophylactic treatment with factor IX impractical, especially if you need several infusions per week to prevent bleeding. Some people with hemophilia B also develop neutralizing antibodies that block the action of factor IX. These are known as inhibitors, which make treatment with factor IX less effective.
To improve treatment options, researchers have developed new factor IX products and other therapies.
Read on to learn about the latest research findings and new treatments for this condition.
The first factor IX products were derived directly from human blood or plasma.
Later, scientists developed recombinant factor IX (rFIX) products, which are genetically modified in the laboratory.
The Food and Drug Administration (FDA) approved the first rFIX product in the 1990s.
In recent years, scientists have modified rFIX to create products with extended half-lives. These products last longer in your body than rFIX products with a standard half-life. This means you need less frequent doses.
The FDA has approved several rFIX products with extended half-lives, including:
- eftrenonacog alfa (Alprolix; rFIX-Fc), approved in 2014
- albutrepenonacog alfa (Idelvion; rFIX-FP), approved in 2016
- nonacog beta pegol (Rebinyn; N9-GP), approved in 2017
All of these products are infused into a vein through an intravenous (IV) line.
Researchers are continuing to study the long-term effects of these products, according to a
Scientists are also developing and testing other rFIX products with an extended half-life, including dalcinonacog alfa (DalcA). This product is injected under your skin.
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Factor IX isn’t the only protein that helps your blood clot. Some hemophilia B treatments increase the availability or action of other clotting factors to help stop bleeding without factor IX.
These include recombinant factor VIIa (rFVIIa). Your doctor may prescribe rFVIIa to treat and prevent bleeding episodes if you have factor IX inhibitors.
The FDA has approved two rFVIIa products to treat hemophilia B:
- NovoSeven RT, approved in 1999
- eptacog beta (SEVENFACT), approved in 2020
SEVENFACT is currently only approved for adults and adolescents ages 12 and older, but recent research suggests it may also be safe and effective for younger people.
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Researchers are also developing rFVIIa products with an extended half-life that last longer in your body than NonoSeven RT or SEVENFACT. These products include MOD-5014 and marzeptacog alfa.
Research on these products is ongoing.
Antithrombin is a protein that blocks the action of factor Xa, as well as factor IXa.
Fitusiran is an experimental drug that lowers antithrombin levels. This promotes blood clotting and limits bleeding.
In 2022, researchers reported the results of two phase 3 clinical trials of fitusiran at a conference of the International Society of Thrombosis and Hemostasis. They found that monthly doses of fitusiran were linked to fewer bleeding episodes in people with hemophilia A or B. Those taking fitusirin also needed fewer doses of clotting factor to treat bleeding.
Studies have shown that fitusirin works in people who have factor IX inhibitors, as well as those who don’t.
The FDA has not yet approved fitusirin for the treatment of hemophilia A or B.
Researchers continue to study it to learn more about its effectiveness, safety, and ideal dosage.
Tissue factor pathway inhibitor (TFPI) is another protein that limits the action of clotting factor Xa.
Concizumab is an injectable monoclonal antibody that blocks TFPI. Blocking TFPI allows your body to produce more Xa, which helps your blood clot even without factor IX.
Phase 1 and 2 clinical trials found concizumab to be effective in reducing bleeding in people with hemophilia A or B, report the authors of a
Concuzimab may be a treatment option for people with factor IX inhibitors, as well as those without.
Phase 3 clinical trials of concizumab are ongoing.
Researchers are also studying other anti-TFPI antibodies, including:
- befovacimab (BAY-1093884)
- marstacimab (PF-06741086)
- MG1113
More research is needed to assess the safety and effectiveness of these drugs.
Gene therapy corrects genetic mutations that cause certain diseases.
In this therapeutic approach, a doctor uses a modified virus to deliver non-defective genes into cells in your body. They can also suppress or inactivate defective genes.
Successful gene therapy for hemophilia B could provide long-term or potentially permanent benefits by replacing your F9 gene with a non-defective gene. This would allow your body to produce enough factor IX on its own, with little or no factor IX infusions.
Scientists have studied several gene therapy approaches to treat hemophilia B. Some of these approaches have shown promise in clinical trials.
For example, researchers found that gene therapy increased circulating factor IX levels by up to
Gene therapy is not yet available to treat hemophilia outside of clinical trials.
More research is needed to investigate its long-term safety and effectiveness.
Getting treatment for hemophilia B is important for preventing and managing bleeding episodes, reducing your risk of complications, and improving your quality of life.
Factor IX replacement and prophylactic therapy are the primary treatments for this condition. Some people develop inhibitors that make these treatments less effective.
New and experimental therapies can help improve treatment options, including for people with and without inhibitors.
Talk to your doctor to learn more about current and emerging treatment options. In some cases, they might encourage you to join a clinical trial to receive an experimental treatment that has not yet been approved.
Your doctor can help you learn more about the potential benefits and risks of different treatments for hemophilia B, including experimental treatments.