ZOLGENSMA 2 x 10^13 VECTOR GENOMES/ML SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Zolgensma 2 x 1013vector genomes/ml solution for infusion

onasemnogene abeparvovec

This medicine is subject to additional monitoring, which will allow for quicker identification of new safety information. You can help by reporting any side effects your child may have. The last section of this leaflet includes information on how to report side effects.

Read all of this leaflet carefully before your child is given this medicine, because it contains important information.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your child's doctor or nurse.
• If your child experiences any side effects, talk to your child's doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Zolgensma and what is it used for
2. What you need to know before your child is given Zolgensma
3. How Zolgensma is given
4. Possible side effects
5. Storage of Zolgensma
6. Contents of the pack and further information

1. What is Zolgensma and what is it used for

What is Zolgensma

Zolgensma is a type of medicine called gene therapy. It contains the active substance onasemnogene abeparvovec, which contains human genetic material.

What Zolgensma is used for

Zolgensma is used to treat spinal muscular atrophy (SMA), a rare and severe inherited disease.

How Zolgensma works

SMA occurs when there is a lack of or abnormal gene needed to produce a protein called survival motor neuron (SMN) protein. The lack of SMN protein causes the death of the nerves that control the muscles (motor neurons). This leads to muscle weakness and wasting, with eventual loss of movement.

This medicine works by providing a fully functional copy of the SMN gene, helping the body to produce enough SMN protein. The gene is given to the cells where it is needed, using a modified virus that does not cause disease in humans.

2. What you need to know before your child is given Zolgensma

Do not use Zolgensma

• if your child is allergic to onasemnogene abeparvovec or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Your child's doctor will check for antibodies before treatment, to help decide if this medicine is suitable for your child.

Infusion-related reactions and severe allergic reactions

Side effects related to the infusion and severe allergic reactions can occur during or soon after your child receives Zolgensma. Possible signs to look out for include rash with itching, pale skin, vomiting, swelling of the face, lips, mouth or throat (which may cause difficulty swallowing or breathing) and/or changes in heart rate and blood pressure. Tell your child's doctor or nurse immediately if you notice your child has these or any other new signs or symptoms during treatment with Zolgensma or soon after. Before your child is discharged, the doctor will provide you with information on what to do if your child experiences new side effects or if they come back once your child is out of the medical center.

Liver problems

Talk to your child's doctor or nurse before this medicine is given to your child if your child has had liver problems in the past. This medicine may cause an increase in the enzymes (proteins) that the liver produces or damage the liver. Liver damage can become severe, including liver failure and death. After this medicine is given, look out for possible signs in your child such as vomiting, yellowing of the eyes and skin (jaundice), or decreased alertness (for more information, see section 4). Tell your child's doctor immediately if you notice your child develops any symptoms that suggest liver damage.

Your child will have a blood test to check their liver function before starting treatment with Zolgensma. Your child will also have regular blood tests at least 3 months after treatment to check for increases in liver enzymes.

Infection

An infection (e.g. cold, flu, or bronchiolitis) before or after treatment with Zolgensma could lead to more serious complications. Caregivers and people in close contact with the patient should follow guidelines for preventing infectious diseases (e.g. hand hygiene, covering the mouth and nose when coughing/sneezing, limiting contact). It is important to look out for signs of infection such as cough, wheezing, sneezing, runny nose, sore throat, or fever. Tell your child's doctor immediately if you notice your child has symptoms that suggest an infection beforeor aftertreatment with Zolgensma.

Regular blood tests

This medicine may decrease the number of platelets in the blood (thrombocytopenia). It is important to look out for possible signs of low platelet count after your child receives Zolgensma, such as bruising or abnormal bleeding (see also section 4). Most cases of low platelet count occurred in the first three weeks after Zolgensma was given to the child.

Before starting treatment with Zolgensma, your child will have a blood test to check the number of blood cells (including red blood cells and platelets), as well as troponin I levels in their body. Your child will also have a blood test to check their kidney function. Your child will have regular blood tests for some time after treatment to check for changes in platelet levels.

Increased troponin I levels

Zolgensma may increase the levels of a heart protein called troponin I. This can be shown by laboratory tests that your child's doctor will perform as needed.

Abnormal blood clotting in small vessels (thrombotic microangiopathy)

There have been reports of patients who developed thrombotic microangiopathy, usually within the first two weeks of being treated with Zolgensma. Thrombotic microangiopathy is associated with a decrease in red blood cells and platelets, and can be life-threatening. These blood clots can affect your child's kidneys. Your child's doctor may want to perform blood tests (platelet count) and check your child's blood pressure. After your child receives Zolgensma, look out for signs such as easy bruising, seizures (fits), or decreased urine output (for more information, see section 4). If your child has any of these signs, seek urgent medical attention.

Blood, organ, tissue, and cell donation

After Zolgensma is given to your child, your child will not be able to donate blood, organs, tissues, or cells. This is because Zolgensma is a gene therapy medicine.

Other medicines and Zolgensma

Tell your child's doctor or nurse if your child is taking, has recently taken, or might take any other medicines.

Prednisolone

Your child will also be given a corticosteroid like “prednisolone” for 2 months or longer (see also section 3) as part of the treatment with Zolgensma. The corticosteroid will help manage any possible increase in liver enzymes that your child may have after receiving Zolgensma.

Vaccines

Since corticosteroids can affect the immune system (defenses), your child's doctor may decide to delay the administration of some vaccineswhile your child is being treated with corticosteroids. Talk to your child's doctor or nurse if you have any questions.

Zolgensma contains sodium

This medicine contains 4.6 mg of sodium per ml, equivalent to 0.23% of the maximum daily intake of 2 g of sodium recommended by the WHO for an adult. Each 5.5 ml vial contains 25.3 mg of sodium, and each 8.3 ml vial contains 38.2 mg of sodium.

Additional information for parents/caregivers

Advanced SMA

Zolgensma may rescue living motor neurons, but it does not rescue dead motor neurons. Children with less severe SMA symptoms (such as absent reflexes or reduced muscle tone) may have enough living motor neurons and may therefore benefit significantly from treatment with Zolgensma. Zolgensma may not work as well in children with severe muscle weakness or paralysis, breathing problems, or difficulty swallowing, or in children with significant birth defects (e.g. heart defects), including patients with SMA type 0, as there may be limited potential for improvement after treatment with Zolgensma. Your child's doctor will decide if this medicine should be given to your child.

Risk of tumors associated with possible insertion of the vector into DNA

There is a possibility that treatments like Zolgensma could insert into the DNA of human body cells. As a result, due to the nature of the medicine, Zolgensma could contribute to the risk of tumors. You should discuss this with your child's doctor. If a tumor occurs, your child's doctor may ask you to take a sample for evaluation.

Hygiene precautions

The active substance of Zolgensma may be temporarily excreted through your child's bodily waste, called “excretions”. Parents and caregivers should practice good hand hygiene for up to 1 month after Zolgensma is given to the child. Use protective gloves when coming into direct contact with your child's bodily fluids or waste, and then wash your hands thoroughly with soap and warm running water, or a hand disinfectant based on alcohol. Use a double bag to dispose of used diapers and other waste. Disposable diapers can continue to be disposed of with household waste.

You should follow these instructions for at least 1 month after your child's treatment with Zolgensma. Talk to your child's doctor or nurse if you have any questions.

3. How Zolgensma is given

Zolgensma will be given to your child by a doctor or nurse trained in the management of the child's disease.

The doctor will calculate the amount of Zolgensma to be given to your child based on the child's weight. Zolgensma will be given through a vein (intravenously) by a single infusion (drip) over about 1 hour.

Zolgensma will be given to your child ONLY ONCE.

Your child will also be given prednisolone (or another corticosteroid) by mouth, which will be started 24 hours before Zolgensma is given. The dose of corticosteroid will also depend on your child's weight. The doctor will calculate the total dose to be given.

Your child will receive corticosteroid treatment daily for about 2 months after Zolgensma is given, or until their liver enzymes decrease to an acceptable level. The doctor will gradually reduce the dose of corticosteroid until it can be stopped completely.

If you have any further questions, ask your child's doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Seek urgent medical attentionif your child has any of the following serious side effects:

Common(these may affect up to 1 in 10 people):

• bruising or bleeding that lasts longer than usual if the child is injured - these may be signs of a low platelet count.

Uncommon(these may affect up to 1 in 100 people):

• vomiting, yellowing of the eyes and skin (jaundice), or decreased alertness. These may be signs of liver damage (including liver failure).
• easy bruising, seizures (fits), or decreased urine output, these may be signs of thrombotic microangiopathy.
• infusion-related reactions (see section 2, “Warnings and precautions”).

Rare(these may affect up to 1 in 1,000 people):

• severe allergic reactions (see section 2, “Warnings and precautions”).

Talk to your child's doctor or nurse if your child has any other side effects. These may include:

Very common(may affect more than 1 in 10 people)

• increase in liver enzymes seen in blood tests.

Common(may affect up to 1 in 10 people):

• vomiting;
• fever.
• increase in troponin I (a heart protein) seen in blood tests.

Reporting of side effects

If your child experiences any side effects, talk to your child's doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zolgensma

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

This information is intended for healthcare professionals who prepare and administer the medicine.

Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP. The expiry date is the last day of the month shown.

The vials will be transported frozen (at -60°C or lower).

Upon receipt, the vials should be refrigerated immediately at a temperature between 2°C and 8°C, and in the original carton. Treatment with Zolgensma should be started within 14 days of receipt of the vials.

This medicine contains genetically modified organisms. Unused medicine or waste materials should be disposed of in accordance with local guidelines on the handling of biological waste. Since this medicine will be administered by a doctor, the doctor is responsible for the proper disposal of the product. These measures will help protect the environment.

6. Container Contents and Additional Information

Zolgensma Composition

• The active substance is onasemnogene abeparvovec. Each vial contains onasemnogene abeparvovec with a nominal concentration of 2 × 10^13 vector genomes/ml.
• The other ingredients are trometamine, magnesium chloride, sodium chloride, poloxamer 188, hydrochloric acid (for pH adjustment), and water for injectable preparations.

Appearance and Container Contents of the Product

Zolgensma is a clear to slightly opaque solution for infusion, colorless to pale yellow.

Zolgensma may be supplied in vials with a nominal fill volume of 5.5 ml or 8.3 ml. Each vial is for single use only.

Each carton will contain between 2 and 14 vials.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Almac Pharma Services Limited

Finnabair Industrial Estate

Dundalk, Co. Louth

A91 P9KD

Ireland

Novartis Pharmaceutical Manufacturing GmbH

Biochemiestraße 10

6336 Langkampfen

Austria

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu/. There are also links to other websites on rare diseases and orphan medicines.

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This information is intended for healthcare professionals only:

Important: Please consult the summary of product characteristics before using the medicinal product.

Each vial is for single use only.

This medicinal product contains genetically modified organisms. Local regulations for the handling of biological waste should be followed.

Handling

• Zolgensma should be handled aseptically in sterile conditions.
• When handling or administering Zolgensma, personal protective equipment (including gloves, safety glasses, sleeves, and laboratory coat) should be worn. Personnel should not work with Zolgensma if they have cuts or scratches on the skin.
• All spills of Zolgensma should be cleaned up with absorbent gauze pads, and the spill area should be disinfected with a sodium hypochlorite solution, followed by alcohol wipes. All materials used for cleaning should be placed in a double bag and disposed of according to local regulations for the handling of biological waste.
• The disposal of all materials that may have come into contact with Zolgensma (e.g., vials, all materials used for injection, including needles and sterile gauze pads) should be carried out according to local regulations for the handling of biological waste.

Accidental Exposure

Accidental exposure to Zolgensma should be avoided.

In case of accidental skin exposure, the affected area should be washed thoroughly with soap and water for at least 15 minutes. In case of eye exposure, the affected area should be rinsed thoroughly with water for at least 15 minutes.

Storage

The vials should be transported frozen (at -60°C or below). Upon receipt, the vials should be refrigerated immediately at a temperature between 2°C and 8°C, and in the original carton. Treatment with Zolgensma should be initiated within 14 days of receipt of the vials. The date of receipt should be marked on the original carton before storing the medicinal product in the refrigerator.

Preparation

The vials should be thawed before use:

• For packages containing up to 9 vials – thaw for approximately 12 hours in the refrigerator (2°C to 8°C) or 4 hours at room temperature (20°C to 25°C).
• For packages containing up to 14 vials – thaw for approximately 16 hours in the refrigerator (2°C to 8°C) or 6 hours at room temperature (20°C to 25°C).

Do not use Zolgensma without thawing.

Once thawed, the medicinal product should not be re-frozen.

After thawing, gently rotate the Zolgensma vial. DO NOT shake.

Do not use this medicinal product if particles or discoloration are observed once the medicinal product has been thawed and before administration.

After thawing, Zolgensma should be administered as soon as possible.

Administration

Zolgensma should be administered to patients only ONCE.

The dose of Zolgensma and the exact number of vials required for each patient should be calculated based on the patient's weight (see sections 4.2 and 6.5 of the summary of product characteristics).

To administer Zolgensma, withdraw the full dose volume into the syringe. Once the dose volume has been withdrawn into the syringe, it should be administered within 8 hours. Remove all air from the syringe before administering to the patient via intravenous infusion through a venous catheter. It is recommended to insert a secondary catheter (backup) in case of blockage in the primary catheter.

Zolgensma should be administered with a syringe pump, as a single slow intravenous infusion of approximately 60 minutes duration. It should be administered exclusively as an intravenous infusion. It should not be administered as a rapid intravenous injection or bolus. After completion of the infusion, the line should be flushed with a sodium chloride 9 mg/ml (0.9%) solution for injectables.

Disposal

The disposal of unused medicinal product and all materials that have come into contact with it should be carried out according to local regulations for the handling of biological waste.

A temporary excretion of Zolgensma may occur, mainly through bodily waste. The following instructions should be given to caregivers and family members of patients for the proper handling of patient bodily fluids and waste:

• Proper hand hygiene (use of protective gloves and subsequent thorough washing of hands with soap and warm running water, or an alcohol-based hand disinfectant) should be performed when coming into direct contact with patient bodily fluids and waste for at least one month after treatment with Zolgensma.
• Disposable diapers should be placed in double-sealed plastic bags and may be discarded with domestic waste.