1. Am I cured of hemophilia after undergoing gene therapy?
No, gene therapy for hemophilia B does not provide a cure: the mutation responsible for hemophilia B in your genes remains. It is not corrected because AAV gene therapy does not alter the defective FIX gene that caused hemophilia. The AAV vector delivers a functional gene to the liver cells, but this gene does not integrate into the patient’s DNA (except in rare cases). As a result, there is no modification of germ cells (such as sperm cells), meaning hemophilia can still be passed on to future generations.
This therapy allows the patient to produce their own factor IX. If the FIX level becomes high enough to prevent bleeding and prophylaxis can be discontinued, one might feel “cured.” However, it remains essential to continue regular follow-up visits at the hemophilia treatment center to monitor FIX levels, potential inhibitors, liver function, and other parameters. This ensures side effects can be detected and the long-term safety and effectiveness of gene therapy can be assessed.
2. How long will gene therapy remain effective after administration?
This is currently an open question. In studies with hemophilia B patients, it has been observed that 3 to 5 years after receiving gene therapy, average FIX activity remains stable and elevated in most participants.
The patient may always return to prophylactic FIX treatment if necessary—for example, if gene therapy is not successful (no FIX levels high enough to discontinue prophylaxis) or if its effectiveness decreases over time (bleeding occurs again because FIX levels drop after having been sufficient for a while).
3. Will I still need prophylaxis?
In a clinical study involving 54 men with moderate to severe hemophilia B, 96% of patients did not require prophylactic treatment between 1 month and 2 years after administration (the most recent published data). The average FIX level was 36.7 IU/dL, with a minimum of 4.7 IU/dL and a maximum of 99.2 IU/dL.
In another study with a different hemophilia B gene therapy product, 86.7% of patients did not need prophylaxis 15 months after treatment. Two years later, FIX levels ranged from 1 to 123.4 IU/dL among the 39 patients who no longer required prophylaxis.
At present, it is not yet understood why FIX production varies so greatly between individuals. Therefore, it is impossible to predict for each patient who will reach sufficient FIX levels to stop prophylaxis and who will not.
4. Will I still have bleeding episodes?
That depends on several factors: trauma or accidents during physical activities, the effectiveness of the gene therapy, and your individual bleeding tendency.
In clinical studies, it was found that after 2 years, patients maintained average FIX levels of 37 IU/dL (etranacogene dezaparvovec) and 26.5 IU/dL (fidanacogene elaparvovec). These levels correspond to “mild hemophilia,” in which spontaneous bleeding is rare. However, it is important to remember that these are averages: some patients had lower FIX levels, for example 10% or less, and continued to experience bleeding.
5. Can I practice any sport I want?
That will depend on how well the gene therapy works for you. To determine this, your FIX activity will be measured regularly, along with the number of bleeds you may still experience. Together with your doctor, you can discuss which sports are safe for you to practice.
Most sports, with proper preparation, are not inherently risky.
6. Can I still receive FIX if, for example, I need surgery?
Yes, FIX concentrate can be administered to a patient who has undergone gene therapy. Whether additional FIX concentrate is needed depends on the patient’s FIX level (and thus the effectiveness of the therapy in that individual) and on the severity of the surgery. The treating physician will decide.
7. Will my joint pain go away?
Currently, there is very limited data on the effect of gene therapy on (joint) pain. Study results are not yet available. Joints that were already severely damaged before gene therapy will not heal as a result of the treatment.
8. If the effect of gene therapy decreases over time, can I receive it again?
Most likely not. The patient’s body develops antibodies against the AAV vectors, which are administered in large amounts during gene therapy. These antibodies remain in the body. If the same gene therapy were administered again years later, it is highly likely that the newly delivered AAV vectors would be immediately attacked and destroyed by those antibodies, rendering the treatment ineffective.
Since it is thought that antibodies against certain AAV vectors (e.g., AAV5) may also neutralize other types (e.g., AAV8 or AAV3), it is not yet known whether another AAV-based therapy would be effective.
For this reason, at present, a second dose is not permitted. Gene therapy is considered a one-time treatment opportunity. Research is ongoing to assess the possibility of re-administration
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