HEMGENIX 1x10E13 GENE COPIES/ML CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you use Hemgenix

Do not use Hemgenix

• If you are allergic to etranacog alfa pegol or any of the other ingredients of this medicine (listed in section 6).

• If you have an active infection, either an acute (short-term) or chronic (long-term) infection, that cannot be controlled with medicines.

• If your liver is not working properly due to advanced liver fibrosis (scarring and thickening of tissue) or cirrhosis (scarring caused by prolonged liver damage).

If any of the above applies to you, or if you are not sure, consult your doctor before receiving Hemgenix.

Warnings and precautions

Before receiving treatment with Hemgenix

Your doctor will perform several tests beforeadministering Hemgenix treatment.

Blood tests to detect antibodies

Before receiving Hemgenix treatment, your doctor will perform blood tests to check for the presence of certain antibodies (proteins), including:

• Blood tests to check for antibodies in the blood against human factor IX protein (factor IX inhibitors).

If you test positive for these antibodies, another test will be performed about 2 weeks later. If both tests are positive, Hemgenix treatment will not be started.

• A blood test may also be performed to check for antibodies in your blood against the type of virus used to make Hemgenix.

Liver health

When deciding if this medicine is suitable for you, your doctor will check your liver health before starting Hemgenix treatment and will:

• Perform blood tests to check liver enzyme levels in the blood.
• Perform a liver ultrasound.
• Perform elastography tests to check for scarring or thickening of the liver.

During or shortly after Hemgenix infusion

Your doctor will monitor you during or shortly afterHemgenix infusion.

Infusion-related reactions

During or shortly after you receive the Hemgenix infusion (drip), infusion-related side effects may occur. Your doctor will monitor you during the Hemgenix infusion and for at least 3 hours after you receive Hemgenix.

• The symptoms of these side effects are listed in section 4 "Possible side effects". Tell your doctor or nurse immediatelyif you experience these or any other symptoms during or shortly after the infusion.

• Depending on your symptoms, your infusion may be slowed down or stopped. If the infusion is stopped, it may be restarted at a slower rate when the infusion reaction has resolved. Your doctor may also consider whether you should receive corticosteroids (e.g. prednisolone or prednisone) to help control the infusion reaction.

After Hemgenix treatment

AfterHemgenix treatment, your doctor will continue to monitor your health.

Liver enzymes

Hemgenix will trigger a response within your immune system that may cause an increase in the blood levels of certain liver enzymes, called transaminases (transaminitis). Your doctor will periodically check your liver enzyme levels to ensure the medicine is working as it should:

• During the first 3 months after you receive Hemgenix, you will have blood tests at least once a week to check your liver enzyme levels.

• If you experience an increase in liver enzymes, you may need to have blood tests more frequently to check your liver enzyme levels until they return to normal. You may also need to take another medicine (corticosteroids) to control these side effects.

• Your doctor may also perform additional tests to rule out other causes of increased liver enzymes, if necessary, after consulting a liver disease specialist.

• Your doctor will repeat liver enzyme tests every 3 months from month 4 to 1 year after you receive Hemgenix to continue monitoring your liver health. In the second year after receiving Hemgenix, your doctor will check your liver enzyme levels every 6 months. After the second year, your doctor will check your liver enzyme levels once a year for at least 5 years after you receive Hemgenix.

Factor IX levels

Your doctor will periodically check your factor IX levels to determine if Hemgenix treatment has worked.

• For at least the first 3 months after you receive Hemgenix, you will have blood tests once a week to check your factor IX levels.

• Your doctor will repeat these tests every 3 months from month 4 to 1 year after you receive Hemgenix to continue monitoring your factor IX levels. In the second year after receiving Hemgenix, your doctor will check your factor IX levels every 6 months. After that, your doctor will check your factor IX levels once a year for at least 5 years after you receive Hemgenix.

• If you experience an increase in liver enzymes or need to take another medicine (e.g. corticosteroids), you will have blood tests more frequently to check your factor IX levels until your liver enzyme levels return to normal or until you stop taking the additional medicine.

Use of other haemophilia treatments

After using Hemgenix, discuss with your doctor whether you should stop other haemophilia treatments you are receiving and when, and develop a treatment plan for what to do in case of surgery, trauma, bleeding, or any procedure that may increase the risk of bleeding. It is very important to continue monitoring and visiting your doctor to determine if you need to receive other haemophilia treatments.

Abnormal blood clotting (thromboembolic events)

After Hemgenix treatment, your factor IX protein level may increase. In some patients, it may increase to above normal levels for a period of time.

• Unusually high factor IX levels may cause your blood to clot abnormally, increasing the risk of forming clots, such as in the lung (pulmonary thromboembolism) or in a leg blood vessel (venous or arterial thrombosis). This theoretical risk is low due to your congenital deficiency in the coagulation cascade compared to healthy subjects.

• You may be at risk of abnormal blood clotting if you already have cardiovascular problems (e.g. history of heart disease, thickening and hardening of the arteries, high blood pressure) or if you are diabetic or over 50 years old.

• Your doctor will periodically check your blood to detect any potential abnormality in factor IX levels, particularly if you continue to receive your routine prophylaxis with factor IX (factor IX replacement therapy) after Hemgenix administration (see also section 3 "How to use Hemgenix").

• Tell your doctor immediately if you notice signs of abnormal clotting, such as sudden chest pain, shortness of breath, sudden muscle weakness, loss of sensation and/or balance, decreased alertness, difficulty speaking, or swelling of one or both legs.

Avoiding blood donations and donations for transplants

The active substance in Hemgenix may be temporarily excreted through blood, semen, breast milk, or body waste, a process called excretion (see also section 2 "Pregnancy, breastfeeding and fertility").

To ensure that other people without haemophilia B are not exposed to the factor IX gene from Hemgenix treatment through the excretion process in your body and/or semen, you must not donate blood, semen, or organs, tissues, or cells for transplants after being treated with Hemgenix.

Immunocompromised patients or patients with HIV or other infections

If you have problems with your immune system (you are immunocompromised), are undergoing or will undergo treatment that suppresses your immune system, or have an HIV infection or other new or recent infection, your doctor will decide when you can receive Hemgenix.

Neutralising antibodies against factor IX proteins (factor IX inhibitors)

Neutralising antibodies against factor IX proteins may prevent Hemgenix from working correctly. Your doctor may check your blood for these antibodies if bleeding is not controlled or recurs after you receive Hemgenix (see also section 3 "How to use Hemgenix").

Receiving gene therapy again in the future

After receiving Hemgenix, your immune system will produce antibodies against the AAV vector envelope. It is not yet known if Hemgenix treatment can be repeated, or under what conditions. It is also not yet known if another gene therapy can be used later, or under what conditions.

Potential risk of malignancy associated with Hemgenix

• Hemgenix will be inserted into liver cells and may be inserted into the DNA of liver cells or other body cells. Therefore, Hemgenix may contribute to an increased risk of cancer, such as liver cancer (hepatocellular carcinoma). Although there is no evidence of this in clinical studies, it is still possible due to the nature of the medicine. You should discuss this with your doctor.

• If you are a patient with pre-existing risk factors for hepatocellular carcinoma (e.g. you have liver fibrosis, hepatitis B, hepatitis C, or non-alcoholic fatty liver disease, or you drink excessive alcohol), your doctor will periodically evaluate (e.g. once a year) your long-term liver health for at least 5 years after Hemgenix administration and will perform the following tests:

• Annual liver ultrasound and
• Annual blood tests to check for increased alpha-fetoprotein.

• After Hemgenix treatment, you are expected to be included in a follow-up study to help study the long-term safety of the treatment (15 years), its efficacy, and any side effects that may be related to the treatment. In case of cancer, your doctor may take a sample of your cancer (biopsy) to check if Hemgenix has been inserted into the cellular DNA.

Children and adolescents

Hemgenix has not been studied in children or adolescents under 18 years of age.

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 medicines that are known to harm the liver (hepatotoxic medicines), your doctor may decide that you need to stop taking this medicine to receive Hemgenix.

Pregnancy, breastfeeding and fertility

There are no data on the use of Hemgenix in women with haemophilia B.

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using Hemgenix.

• Treatment with Hemgenix is not recommended in women who may become pregnant.

It is not yet known if Hemgenix can be used safely in these patients, as the effects on pregnancy and the foetus are unknown.

• Hemgenix must not be used during pregnancy. It is not known if this medicine may have harmful effects on the foetus when administered during pregnancy.

• Hemgenix must not be used during breastfeeding. It is not known if this medicine is excreted in breast milk. A risk to newborns/infants cannot be excluded.

Use of contraceptive methods to avoid pregnancy in the partner for a period of time

After a male patient has been treated with Hemgenix, the patient and his female partner must avoid pregnancy for 12 months. They should use effective contraceptive methods (e.g. double-barrier contraceptives such as condoms and diaphragms). They should do this to avoid the theoretical risk that the factor IX gene from Hemgenix treatment may be transmitted to their child with unknown consequences. For the same reason, male patients must not donate semen. Consult your doctor about which contraceptive methods are suitable.

Driving and using machines

Hemgenix has a minor influence on the ability to drive and use machines. Dizziness, fatigue, and temporary headaches have occurred shortly after Hemgenix infusion. If this happens to you, proceed with caution until you are sure that Hemgenix does not negatively affect your ability to drive or use machines. Discuss this with your doctor.

Hemgenix contains sodium and potassium

• The medicine contains 35.2 mg of sodium (main component of cooking/table salt) per vial. This is equivalent to 1.8% of the maximum recommended daily intake for an adult.

• This medicine contains less than 39 mg (1 mmol) of potassium per vial, so it is essentially "potassium-free".

3. How to use Hemgenix

You will be given Hemgenix in a hospital setting under the supervision of a doctor with experience and training in the treatment of your condition, haemophilia B.

You will receive Hemgenix once onlythrough a single slow infusion (drip) into a vein. The infusion will normally take between 1 and 2 hours to complete.

Your doctor will determine the correct dose for you based on your body weight.

Stopping treatment with exogenous factor IX

• It may take several weeks before an improvement in bleeding control is seen after Hemgenix infusion, and you may need to continue your factor IX replacement therapy during the first few weeks after Hemgenix infusion.

• Your doctor will periodically check the activity levels of factor IX in your blood, i.e. once a week for at least the first 3 months, and at regular intervals afterwards, and will decide if you should receive, reduce, or stop your exogenous factor IX treatment and when (see section 2).

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The following adverse effects were observed in clinical studies with Hemgenix.

Very Common(may affect more than 1 in 10 patients)

• Headache
• Increased levels of liver enzymes in the blood (increase in alanine aminotransferase)
• Increased levels of liver enzymes in the blood (increase in aspartate aminotransferase)
• Pseudogrip syndrome
• Increased levels of C-reactive protein, a marker of inflammation
• Perfusion-related reaction (allergic reactions [hypersensitivity], reaction at the perfusion site, dizziness, eye itching [pruritus], skin redness [rubor], pain in the upper abdomen [abdominal], itchy skin rash [urticaria], chest discomfort, and fever)

Common(may affect up to 1 in 10 patients)

• Dizziness
• Feeling of discomfort (nausea)
• Fatigue
• General feeling of discomfort
• Increased levels of bilirubin in the blood, a yellowish substance formed during the breakdown of red blood cells
• Increased blood levels of creatine phosphokinase, an enzyme (protein) found mainly in the heart, brain, and skeletal muscle

Adverse Effect Reporting

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Hemgenix

This information is intended only for healthcare professionals.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the label of the vial and on the carton after EXP.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep the vials in the original packaging to protect them from light.

Dilute before use.

Once diluted with a 9 mg/ml (0.9%) sodium chloride injection solution, Hemgenix can be stored at a temperature between 15 °C and 25 °C, in the infusion bag, protected from light, for a maximum of 24 hours after dose preparation.

Do not use this medicine if you observe particles, cloudiness, or discoloration.

6. Package Contents and Additional Information

Hemgenix Composition

• The active ingredient is etranacogene dezaparvovec. Each ml of etranacogene dezaparvovec contains 1 x 10^13 copies of the gene (cg)/ml.

• The other components (excipients) are sucrose, polysorbate 20, potassium chloride, potassium dihydrogen phosphate, sodium chloride, sodium hydrogen phosphate, hydrochloric acid (for pH adjustment), and water for injectable preparations (see also section 2 "Hemgenix contains sodium and potassium").

This medicine contains genetically modified organisms.

Appearance of Hemgenix and Package Contents

Hemgenix is a concentrate for solution for infusion (sterile concentrate).

Hemgenix is a clear and colorless solution.

Hemgenix is supplied in a vial that contains 10 ml of etranacogene dezaparvovec.

The total number of vials in a finished package corresponds to the dose needed for each patient, based on their body weight, and is indicated on the package.

Marketing Authorization Holder and Manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

D-35041 Marburg

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus: 12/2024

This medicine has been authorized with a "conditional approval". This type of approval means that more information about this medicine is expected to be obtained.

The European Medicines Agency will review the new information about this medicine at least once a year, and this prospectus will be updated as necessary.

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu, and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

On the European Medicines Agency website, you can find this prospectus in all the languages of the European Union/European Economic Area.

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This information is intended only for healthcare professionals:

Important:consult the complete technical data sheet before using it.

Precautions to be taken before handling or administering the medicine

This medicine contains genetically modified organisms (GMOs).

During the preparation and administration of etranacogene dezaparvovec, personal protective equipment such as gloves, safety glasses, protective clothing, and masks should be used.

Preparation of etranacogene dezaparvovec before administration

1. Use aseptic techniques during the preparation and administration of etranacogene dezaparvovec.
2. Use the vial(s) of etranacogene dezaparvovec only once (single-use vial[s]).
3. Verify the required dose of etranacogene dezaparvovec based on the patient's body weight. The total number of vials in each finished package corresponds to the doses needed for each patient based on body weight.
4. Etranacogene dezaparvovec must be diluted with a 9 mg/ml (0.9%) sodium chloride injection solution before administration.

• Extract the calculated dose volume of Hemgenix (in ml) from the 500 ml infusion bag(s) containing a 9 mg/ml (0.9%) sodium chloride injection solution.

The volume to be extracted will vary depending on the patient's body weight.

• For patients <120 kg body weight, extract the volume of 9 mg ml (0.9%) sodium chloride injection solution corresponding to total dose hemgenix (in ml) from one 500 infusion bag.< li>
• For patients ≥ 120 kg body weight, extract the volume of 9 mg/ml (0.9%) sodium chloride injection solution corresponding to the total dose of Hemgenix (in ml) from two 500 ml infusion bags, extracting half of the volume from each of the two 500 ml infusion bags.

• Then, add the required dose of Hemgenix to the infusion bag(s) so that the total volume of each infusion bag is 500 ml.

1. Add the dose of Hemgenix directly to the 9 mg/ml (0.9%) sodium chloride injection solution. Do not add the dose of Hemgenix towards the air in the infusion bag during dilution.
2. Gently turn the infusion bag(s) at least 3 times to mix the solution and ensure a uniform distribution of the diluted product.
3. To avoid foam formation:

• Do not shake the vial(s) of etranacogene dezaparvovec or the prepared infusion bag(s).
• Do not use filter needles during the preparation of etranacogene dezaparvovec.

1. To reduce the risk of spillage and/or aerosol formation, the infusion bag(s) must be connected to a pre-loaded infusion tube with a sterile 9 mg/ml (0.9%) sodium chloride injection solution.
2. The pre-loaded infusion tube with the sterile 9 mg/ml (0.9%) sodium chloride injection solution must be connected to the main intravenous infusion line, also primed with sterile 9 mg/ml (0.9%) sodium chloride injection solution, before use.
3. Use only the 9 mg/ml (0.9%) sodium chloride injection solution, as the stability of etranacogene dezaparvovec has not been determined with other solutions and diluents.
4. Do not infuse the diluted etranacogene dezaparvovec solution in the same intravenous line with any other product.
5. Do not use a central line or port.

Administration

1. The diluted etranacogene dezaparvovec solution must be visually inspected before administration. The diluted etranacogene dezaparvovec solution must be transparent and colorless. If particles, cloudiness, or discoloration are observed in the infusion bag, do not use etranacogene dezaparvovec.
2. After dilution, use the product as soon as possible. Do not exceed the storage time of the diluted product beyond the time specified in section 6.3 of the technical data sheet.
3. Use an integrated filter (in-line) of 0.2 µm made of polyethersulfone (PES).
4. The diluted etranacogene dezaparvovec solution must be administered in a peripheral vein through a separate intravenous infusion line via a peripheral venous catheter.
5. The etranacogene dezaparvovec solution must be infused strictly following the infusion rate(s) provided in section 4.2 of the technical data sheet. Administration must be completed within ≤ 24 hours after dose preparation (see section 4.2 of the technical data sheet).
6. After infusing the entire contents of the infusion bag(s), the infusion line must be flushed with 9 mg/ml (0.9%) sodium chloride injection solution at the same infusion rate to ensure that all of the etranacogene dezaparvovec is administered.

Measures to be taken in case of accidental exposure

In case of accidental exposure, follow local guidelines for pharmaceutical waste.

• In case of accidental exposure to the eyes, rinse them immediately with water for at least 15 minutes. Do not use an alcoholic solution.
• In case of accidental needlestick exposure, encourage bleeding from the wound and wash the injection site thoroughly with water and soap.
• In case of accidental skin exposure, thoroughly clean the affected area with water and soap for at least 15 minutes. Do not use an alcoholic solution.
• In case of accidental inhalation, move the person to fresh air.
• In case of accidental oral exposure, rinse the mouth thoroughly with water.
• In any case, seek medical attention afterwards.

Work surfaces and materials that may have come into contact with etranacogene dezaparvovec must be decontaminated with a suitable virucidal disinfectant (e.g., a disinfectant that releases chlorine, such as hypochlorite containing 0.1% [1000 ppm] available chlorine) after use.

Precautions to be taken for disposal of the medicine

Unused medicine and disposable materials that may have come into contact with Hemgenix (solid and liquid waste) must be disposed of in accordance with local guidelines for pharmaceutical waste. However, the risk of adverse effects on human health after accidental exposure to Hemgenix and environmental risks are considered negligible. Caregivers should be advised on how to properly handle the waste generated by contaminated medical components during the use of Hemgenix.

Work surfaces and materials that may have come into contact with etranacogene dezaparvovec must be decontaminated with a suitable virucidal disinfectant (e.g., a disinfectant that releases chlorine, such as hypochlorite containing 0.1% [1000 ppm] available chlorine) after use and sterilized in an autoclave, if possible.