Our body contains instructions, called genes, that tell the body how to do things like grow or how to make proteins. Proteins are the building blocks for everything that happens in the body. Some diseases or disorders, such as hemophilia or other bleeding disorders, happen when proteins do not work correctly. This treatment works to provide the body with a copy of a working gene. For hemophilia A or B, that is the factor VIII (8) or IX (9) protein.    

To get a new working gene into the body, it must be protected so that the gene does not get broken down before it can start working. The gene is put into a package called a vector. The vectors used in gene therapy are viruses.² The viruses used for gene therapy are changed so that they cannot make you sick. Instead, the virus protects the gene so that it can travel through the body and get into the liver cell. The virus used in gene therapy for hemophilia is the adeno-associated virus (AAV).     

After receiving the infusion of gene therapy, your body will have the instructions for making factor. Gene therapy targets the liver cells which is where factor is produced.² The instructions (genes) are released from the virus into the liver cells, where they tell the liver cells to produce factor.² This factor protein travels in the bloodstream and will allow your body to make a stable blood clot. Here is a list of questions about gene therapy that you can ask your health care provider about to learn more.

While gene therapy is promising, there are many risks that you need to understand. Unlike other treatments for bleeding disorders, gene therapy works differently in every individual, so it is hard to know if it will work for you. The vector can show up in other cells in the body that are not the target liver cells. There is a chance that the genes can change your genetic information if they are inserted into the wrong area.³ Because this is a new therapy, the long-term side effects are unknown. This is a treatment that cannot be undone. This is also a very high-cost treatment and there is uncertainty around what insurance reimbursement might look like. Here is some more information on known risks:   

• One-time only treatment

  • Once you have received gene therapy using an adeno-associated virus (AAV), you will not be able to have another treatment of gene therapy using this same virus, even if your first gene therapy treatment does not work for you or stops working. The reason gene therapy can be used only one time is that your body will now recognize the virus and attack it if it sees this virus again. When your body attacks the virus, it will cause the virus to be unable to deliver the gene to the liver. If the gene cannot reach the liver cells, it will be unable to provide the instructions needed to make factor.

• Potential damage to the liver

  • Once you have gene therapy, you will need to be closely monitored by your health care provider. You will have your blood checked every week for the first three months after your treatment. These weekly blood tests are done to check for any liver damage that may be caused by the gene therapy and to check factor levels to see how well the gene therapy is working⁶. Treatment is given to patients with test results that show stress on the liver due to the gene therapy.

• Potential for an inflammatory response

  • Your body may react to the gene therapy causing an inflammatory response which is your body’s process of fighting against things that could cause harm like infections or injuries. Due to the high dose of viral particles needed to help your body produce factor you may need extra treatment with high dose steroids for a few weeks or months³. Left untreated, this inflammatory response may be dangerous and may lead to a decrease in the production of factor.

• Potential for liver cancer

  • There is a small possibility that the DNA used for your gene therapy treatment will go to areas of the body where it does not belong. The result of this can be liver cancer in some cases³. If you have an increased risk for liver cancer (including cirrhosis, hepatitis B or C, non-alcoholic fatty liver disease, or chronic alcohol consumption), you should receive annual abdominal ultrasound screenings and blood tests to check your liver the first five years after treatment.  

If you want more information about gene therapy, please go to Future Therapies | Frequently Asked Questions | National Bleeding Disorders Foundation  

1. Hemgenix (etranacogene dezaparvovec) dosing, indications, interactions, adverse effects, and more. (2023). https://reference.medscape.com/drug/hemgenix-etranacogene-dezaparvovec-4000307   

2. Doshi, B. S., & Arruda, V. R. (2018). Gene therapy for hemophilia: what does the future hold? Therapeutic Advances in Hematology, 9(9), 273–293. https://doi.org/10.1177/2040620718791933   

3. Monahan, P. E., Negrier, C., Tarantino, M. D., Valentino, L. A., & Mingozzi, F. (2021). Emerging immunogenicity and genotoxicity considerations of Adeno-Associated virus vector gene therapy for hemophilia. Journal of Clinical Medicine, 10(11), 2471. https://doi.org/10.3390/jcm10112471   

4. Nathwani, A. C. (2019). Gene therapy for hemophilia. Hematology, 2019(1), 1–8. https://doi.org/10.1182/hematology.2019000007   

5. Krumb, E., Lambert, C., & Hermans, C. (2021). Patient selection for hemophilia gene therapy: Real‐life data from a single center. Research and Practice in Thrombosis and Haemostasis, 5(3), 390–394. https://doi.org/10.1002/rth2.12494   

6. Research Human Gene Therapy for Hemophilia. U.S. Food And Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-hemophilia   

7. Roctavian (valoctocogene roxaparvovec) dosing, indications, interactions, adverse effects, and more. (n.d.). https://reference.medscape.com/drug/roctavian-valoctocogene-roxaparvovec-4000066