Hemophilia B is a genetic disorder that affects how well your blood clots. Treatment includes supplementing the protein factor IX, but new therapies may offer alternative ways to manage factor IX deficiency.

Hemophilia is a broad term that describes a group of genetic bleeding disorders that affect the blood’s ability to form clots.

Hemophilia B is caused by a genetic alteration of the F9 gene on the X chromosome, which leads to a deficiency in clotting factor IX. Without enough factor IX, blood clots take longer to form, are fragile, and break down faster, resulting in incomplete bleeding control.

Replacing factor IX is the primary treatment for hemophilia B, but research using novel agents and genetic modification is showing promise.

Replacing missing factor IX has been the mainstay treatment for hemophilia B for many years. Adding factor IX back into your body helps stabilize the clotting sequence.

Recombinant factor IX is synthetic or manmade. Using DNA recombinant technology, host cells in a laboratory are genetically modified to produce factor IX. The protein is then harvested from those cells for therapeutic use. Your doctor administers recombinant factor IX through an intravenous infusion.

There are 2 types of recombinant factor IX therapies. They’re categorized by their half-life, or how long it takes them to break down in your body:

  • Standard half-life: The protein remains in the body for a similar amount of time compared to natural factor IX.
  • Extended half-life: The protein is modified to last longer in the body to reduce the frequency of infusions.

As many as 75% of people with hemophilia B are treated with recombinant factor IX therapy.

If you live with severe hemophilia B, factor IX replacement therapy may be prophylactic or routine. This means you would receive infusions on a set schedule to reduce the risk of major bleeding episodes. Extended half-life therapies are typically used in hemophilia B prophylaxis to prolong the time between treatments.

For mild hemophilia B, factor IX replacement may only take place during a bleeding episode for what’s called “acute management.” Depending on your symptoms and diagnosis, acute management may involve standard half-life therapies since the need for infusions is less frequent.

Factor IX can be directly obtained from human blood or from plasma donations purified in a laboratory setting. Donated blood is painstakingly screened for bloodborne infectious agents, like HIV and hepatitis C, and then further purified through viral inactivation processes.

Plasma-derived factor IX concentrates are grouped into highly purified and intermediate-purity plasma-derived products. Highly purified products primarily contain factor IX, while intermediate purity products may have several other clotting factors.

Despite the rigorous monitoring and filtration process involved in making plasma-derived factor IX concentrates, there is still a small risk of the transmission of bloodborne pathogens. These products are not typically recommended in the United States for the treatment of factor IX deficiency.

Your doctor may recommend a plasma-derived product if:

  • there’s a shortage of recombinant options
  • factor IX is needed in an emergency situation
  • the cost of recombinant treatments is an issue
  • you’ve developed antibodies (known as inhibitors) to a current recombinant regime

Factor IX exists naturally in unmodified human plasma that’s obtained from donors. It’s not virally inactivated, however, and is only used to treat hemophilia B if factor IX concentrates aren’t available.

Fresh frozen plasma isn’t as efficient in raising and maintaining your factor IX levels, which is another reason it isn’t a commonplace treatment.

Blood transfusions can be used to manage secondary complications from hemophilia B.

Transfusions are the administration of whole blood or blood concentrates like red blood cells, platelets, or plasma, which may be necessary if bleeding episodes have caused major blood loss.

Novel agents are emerging therapies that can’t be grouped within the standard treatments for a condition. For hemophilia B, several novel therapies are being investigated, including:

  • Non-factor replacement therapies (fitusiran): Therapies that use non-clotting factor molecules to enhance thrombin generation and fibrin production, the structural foundations of blood clots.
  • Anti-TFPI inhibitors (concizumab): Antibodies that inhibit the substance tissue factor pathway inhibitor (TFPI), which regulates the clotting process. When TFPI is blocked, thrombin and fibrin production can increase.
  • Bypassing agents (FEIBA, NovoSeven, and SevenFact): These are used to initiate clotting through alternative routes when the body has developed inhibitors to traditional therapies.

More novel therapies for hemophilia B are currently being researched. If you’re interested in participating in a clinical trial for one of these treatments, you can explore different opportunities by visiting ClinicalTrials.gov.

In hemophilia B, gene therapy focuses on encoding a functional factor IX protein gene within the cells of your liver. How this is accomplished varies depending on the gene modification involved.

Many gene therapies use vectors, or particles, that act as vehicles to transport genetic material to a location within a cell. Adeno-associated virus (AAV) vectors are a common choice in emerging gene therapy for hemophilia B.

Phase 3 of the HOPE-B clinical trial, which evaluated AAV vector-transported variant etranacogene dezaparvovec for hemophilia B, found it was superior in outcomes to prophylactic factor IX therapy and had favorable safety profiles.

Other gene therapies in research use regulatory elements, known as promoters, insulators, and enhancers, to influence how the factor IX gene is expressed.

Experimental RNA-based approaches are another area of investigation. These approaches use small RNA particles to precisely correct genetic alterations, enhance factor IX production, or switch off other genetics that compete with the clotting process.

Using standard factor IX replacement therapies, most people can achieve an average life span and a good quality of life overall.

Your individual outcome will depend on factors like the severity of hemophilia B, treatment adherence, the development of inhibitors, and individual responses to therapy.

In general, the success rate and outlook for novel treatments and genetic therapies remain unknown. More large-scale research is necessary to determine their long-term safety, efficacy, and accessibility.

Hemophilia B is a blood clotting disorder caused by an alteration in your F9 gene leading to clotting factor IX deficiency.

While factor IX replacement therapy is the standard treatment for this condition, new therapies are currently in research. Novel treatments, like bispecific antibodies and genetic therapy, could one day offer alternative options for hemophilia B management.