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PubMed This is a summary of 24 peer-reviewed journal articles Updated
Hematology

Beyond the Vein: Non-Factor & Gene Therapies

At a Glance

Novel hemophilia treatments include non-factor therapies (like emicizumab and fitusiran) that rebalance blood clotting via subcutaneous injections, and gene therapies (like Hemgenix and Roctavian) that deliver healthy clotting genes to the liver to reduce or eliminate the need for IV infusions.

We are currently in a “Golden Age” of hemophilia treatment. For decades, the only option was replacing the missing factor through frequent intravenous (IV) infusions. Today, new “novel therapies” are changing how we treat this condition by either mimicking the missing factor, rebalancing the blood’s clotting system, or even correcting the underlying genetic cause [1][2].

Non-Factor Therapies: Bypassing the Problem

Non-factor therapies are unique because they do not contain actual Factor VIII or IX. Instead, they use different biological mechanisms to help the blood clot. Most are given as a subcutaneous injection (under the skin) rather than through a vein [3][4].

Emicizumab (Hemlibra)

Emicizumab is a bispecific antibody. Think of it as a bridge-builder [3].

  • How it works: In a healthy body, Factor VIII acts as a bridge between Factor IXa and Factor X to trigger a clot. Emicizumab is engineered to mimic this bridging action [3][5].
  • The Benefit: It is FDA-approved and widely used as a standard, highly effective preventative treatment (prophylaxis) for patients with Hemophilia A, both with and without inhibitors [6][7]. Because it is not actually Factor VIII, it does not trigger the same immune response, making it a revolutionary option for maintaining consistent protection.

Fitusiran

Fitusiran (approved in July 2026) uses a technology called RNA interference (RNAi) to “rebalance” the clotting system [8].

  • How it works: Our blood has natural “brakes” called antithrombin that stop us from clotting too much. Fitusiran lowers the amount of antithrombin in the body, which allows the blood to clot more easily, even if Factor VIII or IX is missing [8][9].
  • The Benefit: It is given just once a month or even once every two months, offering a significant reduction in treatment frequency [4][10].

Gene Therapy: Correcting the Source

Gene therapy aims to turn the body into its own “factor factory.” It uses a harmless virus (an AAV vector) to deliver a healthy copy of the Factor VIII or IX gene directly to the liver cells [11][12].

  • Etranacogene dezaparvovec (Hemgenix): Approved for Hemophilia B, this therapy has shown the ability to provide sustained, near-normal Factor IX levels for years after a single infusion [13][14].
  • Valoctocogene roxaparvovec (Roctavian): Approved for Hemophilia A, this therapy significantly reduces bleeds and the need for infusions [15][16].

The “Unsolved” Questions

While gene therapy is a major breakthrough, there are still important considerations:

  1. Pre-existing Antibodies: Because gene therapy uses an AAV virus as a delivery vehicle, many people who have been exposed to natural AAV viruses in their lifetime already have antibodies against it. This currently makes some patients ineligible for the treatment [17].
  2. Durability: In Hemophilia A, researchers have observed that factor levels tend to decline slowly over several years. It is not yet certain how long the effect will last for every patient [18][19].
  3. Immune Response: Some patients develop an immune response to the viral vector, which can cause liver enzyme levels to rise (transaminitis). This usually requires a course of steroids to protect the new gene [20][21].
  4. One-Shot Deal: Currently, you can only receive gene therapy once. If your body builds up antibodies to the AAV vector used, you cannot receive a “booster” or a second dose of that same type of therapy later [17][22].

These therapies are rapidly evolving, and your care team will help you weigh the convenience of a one-time treatment against the stability of traditional or non-factor prophylaxis [23][24].

Common questions in this guide

What is a non-factor therapy for hemophilia?
Non-factor therapies are medications that help the blood clot without using actual Factor VIII or IX replacements. Instead of intravenous infusions, these are typically given as subcutaneous injections under the skin and work by mimicking missing factors or rebalancing the clotting system.
How does gene therapy for hemophilia work?
Gene therapy uses a harmless viral vector to deliver a functional copy of the missing clotting factor gene directly to your liver cells. This effectively turns your liver into its own factory to produce the Factor VIII or IX that your body needs to clot properly.
Can I get hemophilia gene therapy more than once?
Currently, gene therapy for hemophilia is a one-time treatment. Once you receive it, your body builds up antibodies against the viral vector used to deliver the new gene, meaning you cannot receive a booster or second dose of that same therapy in the future.
Why might someone be ineligible for hemophilia gene therapy?
Gene therapies use a harmless AAV virus as a delivery vehicle. If you have been naturally exposed to similar viruses during your lifetime, your body may already have antibodies that would attack the vector, making the therapy ineffective. Blood tests can determine your eligibility.
How does Fitusiran treat hemophilia?
Fitusiran uses RNA interference technology to lower the amount of antithrombin in your body. Antithrombin acts as a natural brake on blood clotting, so reducing it allows your blood to clot more easily, even if you are missing Factor VIII or IX.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Am I a candidate for Emicizumab based on my current bleed profile and lifestyle goals?
  2. 2.What are the specific risks of 'thrombosis' with Fitusiran, and how will my antithrombin levels be monitored?
  3. 3.How do we test for AAV neutralizing antibodies to see if I am eligible for gene therapy?
  4. 4.If I choose gene therapy for Hemophilia A, what is the current data on how long the Factor VIII expression will last?
  5. 5.What kind of liver monitoring (e.g., blood tests or ultrasounds) is required after receiving gene therapy?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (24)
  1. 1

    Nothing short of a revolution: Novel extended half-life factor VIII replacement products and non-replacement agents reshape the treatment landscape in hemophilia A.

    Abdelgawad HAH, Foster R, Otto M

    Blood reviews 2024; (64()):101164 doi:10.1016/j.blre.2023.101164.

    PMID: 38216442
  2. 2

    Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B.

    Cuker A, Kavakli K, Frenzel L, et al.

    The New England journal of medicine 2024; (391(12)):1108-1118 doi:10.1056/NEJMoa2302982.

    PMID: 39321362
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    Emicizumab prophylaxis in patients with haemophilia A with and without inhibitors.

    Ebbert PT, Xavier F, Seaman CD, Ragni MV

    Haemophilia : the official journal of the World Federation of Hemophilia 2020; (26(1)):41-46 doi:10.1111/hae.13877.

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    Fitusiran: A Novel Antithrombin-Targeting Therapy for Hemophilia A and B, With or Without Inhibitors.

    Alashqar MT, Nahata MC

    The Annals of pharmacotherapy 2026; (60(7)):700-709 doi:10.1177/10600280251403512.

    PMID: 41450180
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    Emicizumab: Review of the literature and critical appraisal.

    Rodriguez-Merchan EC, Valentino LA

    Haemophilia : the official journal of the World Federation of Hemophilia 2019; (25(1)):11-20 doi:10.1111/hae.13641.

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    European principles of inhibitor management in patients with haemophilia: implications of new treatment options.

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    Low immunogenicity of emicizumab in persons with haemophilia A.

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    Rebalancing Hemostasis: Fitusiran as a First-in-Class RNAi Therapy in Hemophilia A and B.

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    An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B.

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    Adeno-associated virus gene therapy for hemophilia: an update meta-analysis and systematic review.

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This page provides educational information on novel hemophilia treatments and gene therapies. It does not replace professional medical advice. Always consult your hematologist to determine the most appropriate and safest treatment plan for your specific condition.

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