Potential Associated Risks

POTENTIAL MEDIUM- AND LONG-TERM RISKS^2,3

There are also some potential risks in the first few weeks, months, and years after infusion.

This might include some side effects that you can’t see or feel. Blood tests are done regularly after gene therapy to check for these.

It is important you are aware of the following risks with HEMGENIX®:

Liver inflammation

HEMGENIX® will trigger a response within your immune system that could lead to an increased level of certain liver enzymes in your blood called transaminases (transaminitis). If this happens, your doctor may prescribe a corticosteroid and you may have more frequent blood tests to check the levels of your liver enzymes, until they return to normal.

DNA Integration

Gene therapy could get into your DNA — a process called integration. Although no evidence of this has been seen in clinical studies, your risk of cancer could increase. Discuss any concerns with your doctor.

Blood clots

The risk of blood clots may be higher. After treatment with HEMGENIX®, your FIX protein level may increase. In some patients, it could increase to levels above the normal range for a period of time. Unusually elevated FIX levels may cause your blood to clot abnormally.

This theoretical risk is low due to your inborn deficiency in the clotting cascade when compared with healthy subjects.

You may be at risk of abnormal blood clotting, if you have preexisting problems with your heart and blood vessels or if you are diabetic or above 50 years.

You should be aware of the signs and symptoms of blood clots, which may include:

• Sudden chest pain
• Shortness of breath
• Swelling in one or both legs
• Loss of sensation and/or balance

Stroke

Blood clots can also lead to stroke. The main signs and symptoms of stroke include:

• Facial drooping on one side of the face
• Weakness or numbness in one arm
• Difficulty speaking

If you experience any symptoms of stroke, call 999 immediately.

Gene therapy fragments

There is also the potential risk of fragments of gene therapy (virus shells) in the blood, semen, breast milk, or bodily waste. To ensure that people without haemophilia B are not exposed to HEMGENIX® DNA through the shedding process in your body and/or semen, you will not be able to donate blood, semen, or organs, tissues and cells for transplantation after you have been treated.

There is also a theoretical risk that gene therapy fragments could be transmitted through sexual activity.

To prevent the theoretical risk that the FIX gene from a father’s HEMGENIX® treatment is transmitted to a child with unknown consequences, you will need to use condoms or another barrier method of contraception for a period of time (up to 1 year) after the gene therapy infusion. Your doctor will advise you on how long you will need to continue using barrier contraception.

Other potential risks

There could also be other risks that are not yet known. Regular appointments are scheduled after your infusion to check that everything is okay.

Your doctor will explain the risks of HEMGENIX® in more detail.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes possible side effects not listed in the package leaflet. You can also report side effects directly via the Yellow Card Scheme. By reporting side effects, you can help provide more information on the safety of this medicine. See below for further information on how to report side effects.

Immune system risk or infections

If you have problems with your immune system (are immunocompromised), are undergoing or will undergo a treatment suppressing your immune system or have an HIV or other new or recent infection, your doctor will decide where you will be able to receive HEMGENIX®.

Antibodies against FIX

Neutralising antibodies against FIX proteins may stop HEMGENIX® from working properly. Your doctor may check your blood for these antibodies, if your bleeds will not be controlled, or return after you have been given HEMGENIX®.

Receiving gene therapy again

After receiving HEMGENIX®, your immune system will produce antibodies to the shell of the AAV vector.

It is not yet known whether or under which conditions therapy with HEMGENIX® may be repeated. It is also not yet known whether or under which conditions subsequent use of another gene therapy may be possible.

Risk of malignancy

HEMGENIX® will insert into liver cells and it could possibly insert into the liver cell DNA or the DNA of other body cells. As a consequence, HEMGENIX® could contribute to a risk of cancer, such as liver cancer (hepatocellular carcinoma).

Although there is no evidence of this in the clinical studies so far, this remains possible because of the nature of the medicine. You should therefore discuss this with your physician.

Children and adolescents

HEMGENIX® has not been studied in children or adolescents under the age of 18.

Other medicines and HEMGENIX®

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. If you are taking medication that are known to damage the liver (hepatotoxic medication), your doctor may decide that you may need to stop this medication to be able to receive HEMGENIX®.

Pregnancy, breast-feeding and fertility

There are no data regarding the use of HEMGENIX® in women with haemophilia B.

If you are pregnant or breast-feeding, think you may be pregnant or plan to become pregnant, ask your doctor for advice prior to be given HEMGENIX®.

HEMGENIX® treatment is not recommended in women who are able to become pregnant or in pregnancy or during breast feeding. It is not yet known whether HEMGENIX® can be used safely in these patients as the effects on pregnancy and the unborn child are not known. It is unknown whether this medicine is excreted in human milk. A risk to newborns or infants cannot be excluded.