Prospect: information for the user

Zolgensma 2 x 1013genomes vectorial/ml solution for perfusion

onasemnogén abeparvovec

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety.You can contribute by reporting any adverse effects your child may have.It is included in the final part of section 4 information on how to report these adverse effects.

Read this prospect thoroughly before this medicine is administered to your child, because it contains important information.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your child's doctor or nurse.
• If your child experiences adverse effects, consult your child's doctor or nurse, even if they are not listed in this prospect, section 4.

What is Zolgensma

Zolgensma is a type of medication called «gene therapy». It contains the active ingredient onasemnogene abeparvovec, which contains human genetic material.

What is Zolgensma used for

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

How Zolgensma works

SMA is caused when there is a lack or abnormal version of a gene necessary to produce an essential protein called the «survival motor neuron» (SMN) protein. The lack of the SMN protein causes the death of the nerve cells that control the muscles (motor neurons). This causes the muscles to weaken and atrophy, eventually leading to a loss of movement.

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

Do not use Zolgensma

• If your child is allergic to onasemnogene abeparvovec or any of the other components of this medication (listed in section6).

Warnings and precautions

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

Liver problems

Speak with your child's doctor or nurse before administering this medication if your child has had any liver problems in the past. This medication may cause an increase in liver enzymes (proteins found in the body) or damage the liver.Liver damage can be severe, including liver failure and death.After administering this medication, watch for signs in your child such as vomiting, jaundice (the whites of the eyes and skin turn yellow), or decreased alertness (see section4). Inform your child's doctor immediately if you notice any symptoms that suggest liver damage.

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

Infection

An infection (e.g., cold, flu, or bronchiolitis) before or after treatment with Zolgensma could cause more severe complications. Caregivers and people in close contact with the patient should follow guidelines for preventing infectious diseases(e.g., hand hygiene, covering coughs/sneezes, limiting contact). It is essential to watch for signs of infection such as cough, wheezing, sneezing, nasal discharge, sore throat, or fever. Inform your child's doctor immediately if you notice any symptoms that suggest an infectionbeforeoraftertreatment with Zolgensma.

This medication may decrease platelet count (thrombocytopenia). It is essential to watch for signs of low platelet count after administering Zolgensma to your child, such as bruises or abnormal bleeding (see section4). Most reported cases of low platelet counts occurred in the first three weeks after Zolgensma was administered to the child.

Zolgensma may increase levels of a heart protein called "troponinI," which can indicate heart damage. It is essential to watch for signs of possible heart problems after administering this medication to your child, such as grayish or bluish skin, difficulty breathing, swelling of arms and legs or abdomen (see section4).

Before starting treatment with Zolgensma, your child will have a blood test to check platelet count and levels of troponinI in the body. They will also have regular blood tests for a period after treatment to detect any changes in platelet count and troponinI levels.

Abnormal coagulation in small blood vessels (microangiopathy)

Cases of patients developing microangiopathy have been reported, usually within the first two weeks of treatment with Zolgensma. Microangiopathy is accompanied by a decrease in red blood cells and cells involved in coagulation (platelets), and can be fatal. These blood clots can affect your child's kidneys. Your child's doctor may want to perform blood tests (platelet count) and monitor blood pressure. After your child receives Zolgensma, watch for signs such as easy bruising, seizures (attacks), or decreased urination (see section4). If your child shows any of these signs, seek urgent medical attention.

Organ donation, blood, tissues, and cells

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

Other medications and Zolgensma

Inform your child's doctor or nurse if they are taking, have taken recently, or may need to take any other medication.

Prednisolone

Your child will also receive a corticosteroid, such as "prednisolone," for 2months or longer (see also section3) as part of the treatment with Zolgensma. The corticosteroid will help manage any possible increase in liver enzymes that your child may experience after administering Zolgensma.

Vaccinations

Since corticosteroids can affect the immune system (defenses),your child's doctor may decide to delay administering some vaccinationswhile your child is receiving corticosteroid treatment. Consult with your child's doctor or nurse if you have any doubts.

Zolgensma contains sodium

This medication contains 4.6mg of sodium per ml, equivalent to 0.23% of the maximum daily intake of 2g of sodium recommended by the WHO for an adult. Each 5.5ml vial contains 25.3mg of sodium, and each 8.3ml vial contains 38.2mg 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 milder SMA symptoms (e.g., absence of reflexes or reduced muscle tone) may have enough living motor neurons, and therefore may benefit significantly from treatment with Zolgensma. Zolgensma may not work as well in children with severe muscle weakness or paralysis, breathing problems, or significant malformations (e.g., heart defects), including patients with SMA type0, as there may be limited potential for improvement after treatment with Zolgensma. Your child's doctor will decide if this medication should be administered.

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

There is a possibility that treatments like Zolgensma could insert themselves into human DNA. Consequently, by the nature of the medication, Zolgensma could contribute to the risk of tumors. You should discuss this with your child's doctor. If a tumor appears, your child's doctor may request a sample for evaluation.

Hygiene care

The active ingredient in Zolgensma may be excreted temporarily through your child's bodily waste, called "excretions." Parents and caregivers should practice good hand hygiene until 1month after Zolgensma is administered to the child. Use protective gloves when having direct contact with fluids or bodily waste from your child, and then thoroughly wash hands with soap and warm running water, or an alcohol-based hand sanitizer. Double-bag the used diapers and other waste. Disposable diapers can be disposed of with household trash.

Follow these instructions for at least 1month after your child's treatment with Zolgensma. Consult with your child's doctor or nurse if you have any doubts.

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

The doctor will calculate the amount of Zolgensma that your child will receive based on the child's weight. Zolgensma will be administered intravenously (into a vein) through a single infusion (drip) over approximately 1 hour.

Zolgensma will be administered to your child only ONCE.

Your child will also receive prednisolone (or another corticosteroid) orally, which will start 24 hours before the administration of Zolgensma. The corticosteroid dose will also depend on your child's weight. The doctor will calculate the total dose to be administered.

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

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

Like all medications, this medication may produce adverse effects, although not all people may experience them.

Seek urgent medical attentionif your child experiences any of the following severe adverse effects:

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

• hematomas or prolonged bleeding if the child has been injured - these may be signs of a decrease in platelets
• grayish or bluish skin color, difficulty breathing (e.g., rapid breathing, lack of air), swelling of arms and legs or abdomen - these may be signs of possible heart problems.

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

• vomiting, jaundice (the whites of the eyes and skin turn yellow), or decreased alertness. These may be signs of liver damage (including hepatic failure).
• easily appearing bruises, convulsions (seizures) or decreased urine production - these may be signs of microangiopathic thrombosis.

Discuss with your child's doctor or nurse if the child experiences any other adverse effect. These may include the following:

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

• increased liver enzymes observed in blood tests.

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

• vomiting;
• fever.

Reporting Adverse Effects

If your child experiences any type of adverse effect, consult with your child's doctor or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly throughthenational reporting system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

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

Do not use this medication after the expiration date that appears on the vial label and on the box after CAD. The expiration date is the last day of the month indicated.

The vials will be transported frozen (at‑60°Corless).

Upon receipt, the vials must be refrigerated immediately to a temperature between 2°Cand8°C, and in the original box. Zolgensma treatment must be initiated within 14days after receipt of the vials.

This medication contains genetically modified organisms. Unused medications or waste materials must be disposed of in accordance with local guidelines for the handling of biological waste. Since a doctor will administer this medication, the doctor is responsible for the correct disposal of the product. These measures will help protect the environment.

Composition of Zolgensma

• The active ingredient is onasemnogene abeparvovec. Each vial contains onasemnogene abeparvovec with a nominal concentration of 2×1013vector genomes/ml.
• The other components are tromethamine, magnesium chloride, sodium chloride, poloxamer 188, hydrochloric acid (for pH adjustment) and water for injection.

Appearance of the product and contents of the package

Zolgensma is a transparent to slightly opaque, colorless to pale white solution for infusion.

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

Each carton will contain between 2 and 14vials.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin4

Irlanda

Responsible Person

Almac Pharma Services Limited

Finnabair Industrial Estate

Dundalk, Co.Louth

A91P9KD

Irlanda

Novartis Pharmaceutical Manufacturing GmbH

Biochemiestraße 10

6336 Langkampfen

Austria

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Alemania

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Alemania

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

Last update of this leaflet

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan drugs.

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This information is intended for healthcare professionals:

Important: Please consult the product information/summary of 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 biohazardous 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 a laboratory coat) should be used. Personnel should not work with Zolgensma if they have cuts or abrasions on their skin.
• Any spills of Zolgensma should be cleaned up with absorbent cotton gauze pads, and the area should be disinfected with a sodium hypochlorite solution, followed by alcohol wipes. All materials used for cleaning should be placed in double-bag, and disposed of in accordance with local regulations for the handling of biohazardous waste.
• 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) should be carried out in accordance with local regulations for the handling of biohazardous waste.

Accidental exposure

Accidental exposure to Zolgensma should be avoided.

In the event of skin exposure, the affected area should be thoroughly cleaned with soap and water for a minimum of 15 minutes. In the event of eye exposure, the affected area should be thoroughly flushed with water for a minimum of 15 minutes.

Storage

Vials should be transported frozen (-60°C or less). Upon receipt, vials should be refrigerated immediately at a temperature between 2°Cand8°C, and in the original carton. Treatment with Zolgensma should be initiated within 14days 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

Vials must be thawed before use:

• For vials containing up to 9vials – thaw for approximately 12hours in the refrigerator (2°C to 8°C) or4hours at room temperature (20°C to 25°C).
• For vials containing up to 14vials – thaw for approximately 16hours in the refrigerator (2°C to 8°C) or 6hours at room temperature (20°C to 25°C).

Zolgensma should not be used without thawing.

Once thawed, the medicinal product should not be refrozen.

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

Zolgensma should not be used 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 is calculated based on the patient's weight (see sections4.2 and 6.5 of the product information/summary of characteristics).

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

Zolgensma should be administered with the syringe pump, as a single intravenous infusion lasting approximately 60minutes. It should be administered exclusively as an intravenous infusion. It should not be administered as a rapid intravenous bolus or as a single dose.

After completion of the infusion, the line should be flushed with sodium chloride 9mg/ml (0.9%) for injection.

Disposal

Disposal of unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations for the handling of biohazardous waste.

Excretion of Zolgensma may occur temporarily, mainly through bodily waste. Caregivers and family members of patients should be given the following instructions for the proper handling of patient fluids and waste:

• Proper hand hygiene (use of protective gloves and thorough hand washing with soap and water or an alcohol-based hand sanitizer) should be followed when coming into direct contact with patient fluids and waste for a minimum of one month after treatment with Zolgensma.
• Disposable diapers should be placed in double-bag, plastic bags, and can be disposed of with household waste.