What drugs are used to treat hemophilia B? A comprehensive guide to medication and therapy

October 14, 2025 •

5 min read

Hemophilia B, a rare genetic disorder affecting about 1 in 30,000 male births, is characterized by a deficiency in blood clotting factor IX. Effective treatment for hemophilia B has evolved significantly, offering several options, including replacement therapies and innovative new drugs designed to improve patient quality of life and manage bleeding episodes.

Quick Summary

Treatment for hemophilia B includes standard and extended half-life factor IX concentrates for prophylaxis or on-demand use, innovative gene therapy like Hemgenix, and non-factor therapies such as Concizumab and Fitusiran. These advanced options aim to reduce bleeding episodes and treatment burden. Ancillary and bypassing agents are also used in specific cases, including for patients with inhibitors.

Key Points

Factor IX Replacement: The standard of care involves infusions of either plasma-derived or lab-made recombinant factor IX concentrates to replace the missing clotting protein.
Extended Half-Life (EHL) Products: Newer factor IX therapies, like Alprolix and Idelvion, are engineered to last longer in the body, enabling less frequent intravenous infusions.
Gene Therapy: Hemgenix is a one-time gene therapy for eligible adults with hemophilia B that delivers a functional gene to the liver, allowing the body to produce its own factor IX.
Non-Factor Therapies: Newer drugs like Concizumab and Fitusiran target the coagulation cascade differently, making them effective for patients who have developed inhibitors to standard factor products.
Treating Inhibitors: For patients who develop inhibitors, bypassing agents such as activated prothrombin complex concentrate (Feiba) are used to manage bleeding episodes.
Prophylaxis vs. On-Demand: Treatment can be administered prophylactically to prevent bleeding or on-demand to stop an acute bleed, with prophylaxis being the standard for severe cases.

Standard Factor IX Replacement Therapy

For decades, the cornerstone of hemophilia B treatment has been factor IX (FIX) replacement therapy. These medications work by introducing commercially prepared clotting factor concentrates into a patient's vein to replace the missing or deficient factor, allowing the blood to clot properly.

There are two primary types of FIX concentrates:

Plasma-derived factor concentrates: These are made from human plasma collected from a large pool of donors. The plasma undergoes multiple testing and treatment processes to ensure viral safety.
Recombinant factor concentrates: Developed using genetic engineering, these lab-made concentrates do not contain human plasma, which completely eliminates the risk of transmitting bloodborne viruses.

Treatment is administered in one of two ways:

Prophylactic care: Regular, scheduled infusions are given to maintain a baseline level of FIX, preventing bleeding episodes from occurring. This is the standard of care for patients with severe hemophilia B.
Episodic or 'on-demand' care: Infusions are given only when a bleeding episode occurs to stop the bleeding. This is more common in patients with mild or moderate hemophilia.

Extended Half-Life (EHL) Factor IX Products

Significant advances in therapy have led to the development of EHL factor IX products. Standard FIX products have a half-life of 18 to 40 hours, requiring infusions multiple times a week. EHL products are designed to last longer in the body, which extends the interval between infusions, reducing the treatment burden for patients. Examples of EHL FIX products include Alprolix, Idelvion, and Rebinyn.

Mechanism: These products are modified using technologies like Fc fusion or PEGylation to extend their circulation time. For example, Alprolix uses Fc fusion technology to recycle the factor IX, mimicking the body's natural processes.
Dosing: With EHL products, many patients can move to once-weekly or even less frequent dosing, which can lead to better treatment adherence and an improved quality of life.

Non-Factor Therapies: Novel Agents for Hemophilia B

Recently, several non-factor therapies have emerged that bypass the need for direct factor replacement by rebalancing the coagulation cascade. These are particularly valuable for patients who have developed inhibitors, meaning their immune system attacks infused factor proteins.

Rebalancing Agents

Concizumab (Alhemo): This monoclonal antibody targets and inhibits tissue factor pathway inhibitor (TFPI), a protein that normally slows down blood clotting. By neutralizing TFPI, it helps enhance thrombin generation and stabilize clots. It is administered via subcutaneous injection and can be used for prophylaxis in patients with or without inhibitors.
Fitusiran (Qfitlia): This is a small interfering RNA (siRNA) that works by inhibiting the synthesis of antithrombin, another protein that limits clotting. By lowering antithrombin levels, fitusiran promotes clot formation. This, too, is a subcutaneous injection used for prophylactic treatment.

Gene Therapy: A Potentially Curative Approach

Gene therapy offers a revolutionary, single-dose treatment option for eligible adults with hemophilia B, aiming for long-term, sustained production of factor IX.

Hemgenix (etranacogene dezaparvovec): Approved by the FDA in November 2022, Hemgenix is an adeno-associated viral (AAV) vector-based therapy. It delivers a functional copy of the F9 gene to liver cells, enabling the body to produce its own factor IX. In clinical trials, it significantly reduced the annualized bleeding rate, with many participants discontinuing prophylactic therapy. While very expensive, its potential long-term benefits may offset the high cost of lifelong prophylaxis.

Adjunctive and Bypassing Agents

Certain situations, like minor bleeding or the presence of inhibitors, require alternative medications.

Antifibrinolytics: Drugs like epsilon-aminocaproic acid (Amicar) and tranexamic acid prevent the breakdown of blood clots once they have formed. They are often used for bleeding in the mouth, nasal passages, or after dental procedures.
Bypassing Agents: For patients who have developed inhibitors, bypassing agents are used to manage bleeding episodes. These agents bypass the need for factor IX (or factor VIII) to activate the coagulation cascade. Examples include activated prothrombin complex concentrates (e.g., Feiba) and recombinant factor VIIa (e.g., NovoSeven RT).

Comparison of Hemophilia B Treatment Options


Feature	Standard Factor IX	Extended Half-Life FIX	Non-Factor Therapies	Gene Therapy (Hemgenix)
Mechanism	Replaces missing FIX directly.	Replaces missing FIX directly; modified for longer circulation.	Modifies the clotting cascade (e.g., inhibits antithrombin/TFPI).	Delivers a functional F9 gene via a viral vector.
Delivery	Intravenous (IV) infusion, several times a week.	IV infusion, once a week or less frequently.	Subcutaneous (SubQ) injection, usually weekly or less often.	One-time IV infusion.
Inhibitor Status	Ineffective if inhibitors develop; requires bypassing agents.	Ineffective if inhibitors develop; requires bypassing agents.	Effective in patients with or without inhibitors.	Effective in patients without AAV5 antibodies.
Benefits	Proven, reliable, standard treatment.	Less frequent infusions, lower treatment burden.	SubQ administration, effective for inhibitor patients, less burdensome.	Potential for durable, long-term FIX production, potentially life-changing.
Drawbacks	Frequent infusions, risk of inhibitor development.	Requires regular infusions, risk of inhibitors still exists.	Novel agents, long-term safety data still emerging, risk of thromboembolism.	High cost, long-term efficacy uncertain, immune response to vector possible.

The Future of Hemophilia B Treatment

The landscape of hemophilia B treatment is rapidly evolving, driven by the desire to reduce treatment burden, improve adherence, and provide better long-term outcomes. Personalized medicine, which tailors a prophylactic regimen based on an individual's specific needs, lifestyle, and pharmacokinetic profile, is becoming increasingly important. While gene therapy offers the potential of a long-term solution, continued research into optimizing its delivery, managing immune responses, and addressing accessibility is essential. Further non-factor therapies are also in development, broadening the options for patients, particularly those with inhibitors. The overall goal remains to move beyond simply managing bleeds toward therapies that offer sustained factor levels and improved quality of life for all people with hemophilia B.

Conclusion

Treatment for hemophilia B has progressed dramatically from frequent plasma-derived factor infusions to a wide range of options that include safer recombinant products, extended half-life versions, and innovative non-factor and gene therapies. The standard of care remains FIX replacement, but advanced therapies offer significant advantages, such as reduced infusion frequency and effectiveness in patients with inhibitors. Gene therapy, such as Hemgenix, presents the exciting prospect of a single-dose, potentially life-long treatment that could significantly improve patient outcomes and quality of life. The choice of treatment is increasingly personalized, balancing a patient's lifestyle, disease severity, and individual needs to ensure the most effective and least burdensome management plan. The ongoing research and development of novel therapies promise an even brighter future for those living with hemophilia B. To stay informed on the latest developments, authoritative sources like the CDC offer reliable resources on hemophilia treatment.

Frequently Asked Questions

Standard factor IX products have a shorter lifespan in the body, typically requiring infusions multiple times per week. EHL products are modified to last longer, which allows for less frequent dosing, such as once a week or less, reducing the treatment burden.

Gene therapy for hemophilia B, such as with the drug Hemgenix, offers a potentially long-term correction of the genetic defect by enabling the body to produce its own factor IX. While often considered life-changing and potentially curative for many patients, long-term durability and safety continue to be monitored.

For hemophilia B patients who develop inhibitors, treatment involves bypassing agents, which promote clotting without requiring factor IX. More recently, non-factor therapies like Concizumab and Fitusiran have been approved for prophylaxis in inhibitor patients.

Most treatments for hemophilia B, including factor replacement and gene therapy, are delivered via intravenous infusion or subcutaneous injection. Currently, there are no approved oral non-injection options, though research into such delivery methods is ongoing.

Rebalancing agents are a new class of non-factor therapies that restore the balance of the blood's clotting system. They work by either inhibiting natural anticoagulants, like antithrombin (Fitusiran) or tissue factor pathway inhibitor (Concizumab), to promote clotting.

Eligibility for Hemgenix is based on specific criteria, including patient's inhibitor status and the presence of antibodies to the viral vector used for delivery. A specialized screening process is required to determine if a patient can receive the treatment.

Antifibrinolytic agents like Amicar and tranexamic acid help to prevent the breakdown of existing blood clots. They are typically used as an adjunctive therapy, especially for managing bleeding in the mouth or after dental extractions.