onasemnogene abeparvovec: package leaflet

Itvisma is a type of medicine called a gene therapy and contains the active substance onasemnogene abeparvovec. A gene therapy product works by delivering a gene into the body to correct a genetic defect. The gene is delivered into the cells where it is needed using a modified virus that does not cause disease in humans.

Itvisma is used to treat 5q spinal muscular atrophy (SMA), a rare, serious inherited disease. It is used in adults, adolescents and children aged 2 years and older with inherited mutations (changes) affecting a gene called SMN1.

SMA occurs when there is a missing or abnormal version of a gene needed to make an essential protein called survival motor neuron (SMN) protein. Lack of SMN protein causes nerves that control muscles (motor neurons) to die. This results in muscles becoming weak and wasting away, with eventual loss of movement.

The active substance in Itvisma, onasemnogene abeparvovec, works by supplying a fully functioning copy of the SMN gene, which then helps the body to produce enough SMN protein for survival and maintenance of motor neurons.

Do NOT use Itvisma
- if you are allergic to onasemnogene abeparvovec or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Your doctor will carry out a test to check for antibodies before treatment to help decide if this medicine is suitable for you.

Liver problems
Talk to your doctor or nurse before this medicine is given if you have had any liver problems. This medicine can lead to an increase in enzymes (proteins) made by the liver, which can be a sign of a problem with the liver, or injury to the liver. Tell your doctor straight away if you notice any symptoms suggestive of liver problems, including:
- vomiting;
- jaundice (yellowing of the skin or of the whites of the eyes), or;
- reduced alertness (see section 4 “Possible side effects”).

You will have a blood test to check how well the liver is working before starting treatment with Itvisma. You will be given a type of medicine called a corticosteroid (for example, prednisolone) to help manage any increase in liver enzymes that may develop after you are given Itvisma (see section 3 “How Itvisma is given”).

You will also have regular blood tests for at least 3 months after treatment to monitor for changes in how your liver is working. These tests will be done more often during the first few weeks after Itvisma administration and while you are on corticosteroid treatment, and less often afterwards, if your liver tests are at an acceptable level.

Regular blood tests
This medicine can lower blood platelet levels (thrombocytopenia). You need to look out for possible signs of a low blood platelet count after you are given Itvisma, such as abnormal bruising or bleeding (see section 4 “Possible side effects”). Most cases of low blood platelet levels occurred within the first week after the patient was given Itvisma.

Before starting treatment with Itvisma, you will have a blood test to check the amount of blood cells (including red blood cells and platelets) in your body. You will also have regular blood tests for a period of time after treatment to monitor for changes in platelets.

Nerve problems affecting sensation of pain, temperature and touch (peripheral sensory neuropathy) Peripheral sensory neuropathy has occurred with Itvisma. Symptoms may occur approximately three weeks after Itvisma is given. Possible signs you need to look out for after you have been given this medicine include numbness, tingling, prickling or pain in the arms, hands, legs and/or feet. Tell your doctor straight away if you develop any of these signs.

Abnormal clotting of blood in small blood vessels (thrombotic microangiopathy)
Thrombotic microangiopathy may occur. Thrombotic microangiopathy is a serious condition where tiny blood clots form in the smallest blood vessels throughout the body. It is associated with thrombocytopenia, a decrease in blood platelets (components that help the blood to clot) and destruction of red blood cells. It can be life-threatening if not treated promptly. These blood clots could affect the kidneys. Your doctor may want to check your blood platelet levels and blood pressure.
Before starting treatment with Itvisma, you will have a blood test to check your creatinine level, which is an indicator of how your kidneys are working. Possible signs you need to look out for after you have been given Itvisma include bruising easily, seizures (fits) or decrease in urine output. Seek urgent medical attention if you develop any of these signs.

Risk of tumours associated with potential insertion into the DNA
There is a possibility that gene therapies such as Itvisma can insert into the DNA of human body cells.
As a consequence, Itvisma could contribute to a risk of tumours because of the nature of the medicine.
You should discuss this with your doctor. In the event of a tumour, your doctor may take a sample for further evaluation.

Infections
An infection (e.g. cold, flu or bronchiolitis) before or after Itvisma treatment may lead to more serious complications. Caregivers and others with whom you are in close contact should follow infection prevention practices (e.g. hand hygiene, coughing/sneezing etiquette, limiting potential contacts). You need to look out for signs of an infection such as coughing, wheezing, sneezing, runny nose, sore throat or fever. Tell your doctor straight away if you notice any symptoms suggestive of infection before or after Itvisma treatment. If you have an infection before Itvisma treatment, your doctor may delay treatment until the infection has resolved.

Blood, organ, tissue and cell donation
After you have been treated with Itvisma, you will not be able to donate blood, organs, tissues or cells.
This is because Itvisma is a gene therapy medicine.

Other medicines and Itvisma
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

Vaccinations
As corticosteroids can affect the body’s immune (defence) system, your doctor may decide to delay giving some vaccinations while you are receiving corticosteroid treatment (see section 3, “How Itvisma is given”). Talk to your doctor or nurse if you have any questions.

Pregnancy and breast-feeding
There is no information on the use of Itvisma in pregnant or breast-feeding women. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, talk to your doctor for advice before being treated with Itvisma.

Driving and using machines
Do not drive or use machines if you experience dizziness (see section 4 “Possible side effects”). Talk to your doctor first.

Itvisma contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per 3 mL dose, that is to say essentially ‘sodium-free’.

The recommended dose of Itvisma is 1.2 × 1014 vector genomes (vg). Itvisma will be given to you ONCE only.

Itvisma will be given to you in a hospital setting under the supervision of a doctor experienced in the management of patients with SMA.

Itvisma is given by injection into the lower back. This injection, called a lumbar puncture, is done by inserting a needle into the space around the spinal cord. You may also be given a medicine to make you relax or sleep during the procedure. Care after you are given Itvisma will be provided by your doctor.

You will also be given prednisolone (or another corticosteroid) by mouth, starting 24 hours before being given Itvisma. The dose of corticosteroid will depend on your weight. Your doctor will work out the total dose to give.

You will be given corticosteroid treatment daily for about 2 months after the dose of Itvisma, or until your liver enzymes decrease to an acceptable level. The doctor will slowly reduce the dose of corticosteroid until treatment can be fully stopped. Tell your doctor if you vomit before or after you take the corticosteroid dose; your doctor can then make sure you are receiving the full dose.

If you have any further questions ask your doctor or nurse.

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

Seek urgent medical attention if you develop any of the following serious side effects:

Common (may affect up to 1 in 10 people)
- bruising or bleeding for longer than usual if you have been hurt – these may be signs of a low blood platelet count (thrombocytopenia)
- nerve problems affecting sensation of pain, temperature, touch (peripheral sensory neuropathy)
- sensations like numbness, tingling, pins and needles (paraesthesia)
- reduced sense of touch or sensation (hypoaesthesia)

Talk to your doctor or nurse if you develop any other side effects. These can include:

Very common (may affect more than 1 in 10 people)
- nose and throat (upper respiratory tract) infection
- fever
- vomiting
- headache

Common (may affect up to 1 in 10 people)
- increases in liver enzymes seen in blood tests
- dizziness

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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

The following information is for healthcare professionals who will prepare and give 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 refers to the last day of that month.

The vial will be transported frozen (at or below -60 °C).

Store in the original carton.

Upon receipt the vial should be refrigerated at 2 °C to 8 °C immediately, and in the original carton.
Itvisma therapy should be initiated within 14 days of receipt of the vial.

Once thawed, the medicinal product should not be re-frozen and may be stored refrigerated at 2 °C to 8 °C in the original carton for 14 days.

Once the dose is drawn into the syringe, it may be held at 2 °C to 8 °C for up to 24 hours, including a 5-hour maximum time out-of-refrigeration allowance within the 24-hour period.

This medicine contains genetically-modified organisms. Unused medicine or waste material must be disposed of in compliance with the local guidelines on handling of biological waste. As this medicine will be given by a doctor, the doctor is responsible for the correct disposal of the product. These measures will help protect the environment.

What Itvisma contains
- The active substance is onasemnogene abeparvovec. Each vial contains 1.2 × 1014 vector genomes onasemnogene abeparvovec in 3 mL solution.
- The other ingredients are tromethamine, magnesium chloride, sodium chloride, poloxamer 188, hydrochloric acid (for pH adjustment) and water for injections (see also section 2 “Itvisma contains sodium”).

What Itvisma looks like and contents of the pack
Itvisma is a clear to slightly opaque, colourless to faint white solution for injection.

Itvisma is supplied in a carton of one vial containing a nominal fill volume of 3 mL. Each vial is for single use only.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestraße 10
6336 Langkampfen
Austria

Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11
Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111
Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf.: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 111

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00
Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888
France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01
Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor ehf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1
Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

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The following information is intended for healthcare professionals only:

Important: Please refer to the Summary of Product Characteristics (SmPC) before using.

Each vial is for single use only.

Handling
- Itvisma should be handled aseptically under sterile conditions.
- Prior to intrathecal injection, Itvisma should be brought to room temperature. Thaw Itvisma in the refrigerator (2 °C to 8 °C) for approximately 4 hours, or at room temperature (20 °C to 25 °C) for approximately 1 hour.
- Itvisma is a clear to slightly opaque, colourless to faint white solution. Do not use this medicinal product if you notice any particles, cloudiness or discolouration once the frozen product has thawed and prior to administration.
- Do not shake.
- Once thawed, the medicinal product should not be re-frozen.
- After thawing, Itvisma should be given as soon as possible. Once the dose volume is drawn into the syringe it may be held in the refrigerator (2 °C to 8 °C) for up to 24 hours, including a 5- hour maximum time out-of-refrigeration allowance within the 24-hour period. Discard the vector-containing syringe if not used within this time period.

Preparation
- This medicinal product contains genetically modified organisms (GMOs).
- Personal protective equipment (including gloves, safety goggles, laboratory coat and sleeves) should be worn while handling or administering Itvisma.
- When assembling the injection, it must be ensured that the components’ surface in contact with Itvisma solution consists of the compatible materials listed in the table below. Device components must be indicated for intrathecal or neuraxial use.

Component materials compatible with Itvisma

Component
Material of construction
18 to 19 G needle for withdrawal, maximum
40 mm long
Stainless steel
5 to 10 mL syringea
Polypropylene
Syringe capa
Polypropylene, polyethylene or methacrylate- acrylonitrile-butadiene-styrene
22 to 27 G spinal needle, maximum 156 mm long
Stainless steel a
Not to be manufactured with polyvinylchloride (PVC), bisphenol-A (BPA), bis(2-ethylhexyl) phthalate (DEHP) or latex

Administration

For intrathecal use. Treatment should be administered intrathecally using a lumbar puncture by healthcare professionals experienced in performing lumbar punctures.

• Immediately prior to dosing, draw the content from the vial into the syringe, remove air from the syringe, confirm the dose volume of 3 mL in the syringe, cap the syringe and deliver to the patient injection location.
• If indicated by the patient’s clinical status, sedation should be considered.
• Imaging techniques to guide intrathecal injection may be considered.
• The patient should be evaluated prior to and after intrathecal injection for the presence of potential conditions related to lumbar puncture, to avoid serious procedural complications.
• Prior to administration, remove 3 mL of cerebrospinal fluid (CSF) using a lumbar puncture needle.

• Itvisma is administered as a single-dose bolus intrathecal injection over approximately 1 to 2 minutes.
• Following intrathecal injection, placement in Trendelenburg position (depending on the patient’s clinical status) is recommended.

Accidental exposure
Accidental exposure to Itvisma must be avoided.

In the event of accidental exposure to skin, the affected area must be thoroughly cleaned with soap and water for at least 15 minutes. In the event of accidental exposure to eyes, the affected area must be thoroughly flushed with water for at least 15 minutes.

All spills of Itvisma must be wiped with absorbent gauze pad and the spill area must be disinfected using a bleach solution followed by alcohol wipes. All clean-up materials must be double bagged and disposed of in accordance with local guidelines on handling of biological waste.

Disposal
All materials that may have come in contact with Itvisma (e.g. vial, all materials used for injection, including sterile drapes and needles) must be disposed of in accordance with local guidelines on handling of biological waste.

What Zolgensma is
Zolgensma is a type of medicine called a ‘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, serious inherited disease.

How Zolgensma works
SMA occurs when there is a missing or abnormal version of a gene needed to make an essential protein called ‘Survival Motor Neuron’ (SMN) protein. Lack of SMN protein causes nerves that control muscles (motor neurons) to die. This results in muscles becoming weak and wasting away, with eventual loss of movement.

This medicine works by supplying a fully functioning copy of the SMN gene which then helps the body produce enough SMN protein. The gene is delivered into 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 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 serious allergic reactions
Infusion-related side effects and serious allergic reactions can occur during, and/or shortly after, your child is given Zolgensma. Possible signs you need to look out for include itchy rash, pale skin, vomiting, swelling of face, lips, mouth or throat (which may cause difficulty in 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 develops these or any other new signs or symptoms during, and/or shortly after, Zolgensma treatment. Before your child is discharged, the doctor will provide you with information on what to do in case your child experiences new side effects or side effects which come back once you leave the medical facility.

Liver problems
Talk to your child’s doctor or nurse before this medicine is given if your child has had any liver problems. This medicine can lead to an increase in enzymes (proteins found within the body) produced by the liver or injury to the liver. Injury to the liver can lead to serious outcomes, including liver failure and death. Possible signs you need to look out for after your child is given this medicine include vomiting, jaundice (yellowing of the skin or of the whites of the eyes), or reduced alertness (see section 4 for more information). Tell your child’s doctor straightaway if you notice your child develops any symptoms suggestive of injury to the liver.

Your child will have a blood test to check how well the liver is working before starting treatment with Zolgensma. Your child will also have regular blood tests for at least 3 months after treatment to monitor for increases in liver enzymes.

Infection
An infection (e.g. cold, flu or bronchiolitis) before or after Zolgensma treatment may lead to more serious complications. Caregivers and close contacts with the patient should follow infection prevention practices (e.g. hand hygiene, coughing/sneezing etiquette, limiting potential contacts). You need to look out for signs of an infection such as coughing, wheezing, sneezing, runny nose, sore throat or fever. Tell your child’s doctor straightaway if you notice your child develops any symptoms suggestive of infection before or after Zolgensma treatment.

Regular blood tests
This medicine can lower blood-platelet counts (thrombocytopenia). You need to look out for possible signs of a low blood-platelet count after your child is given Zolgensma such as abnormal bruising or bleeding (see section 4 for more information). Most of the reported cases of a low blood-platelet count occurred within the first three weeks after the child was given Zolgensma.

Before starting treatment with Zolgensma, your child will have a blood test to check the amount of blood cells (including red blood cells and platelets), as well as troponin-I level in their body. They will also have a blood test to check their creatinine level, which is an indicator of how the kidneys are working. Your child will also have regular blood tests for a period of time after treatment to monitor for changes in platelet levels.

Increased levels of troponin-I (a heart protein)
Zolgensma can raise levels of a heart protein called troponin-I. This can be shown in laboratory tests that your child’s doctor will perform as needed.

Abnormal clotting of blood in small blood vessels (thrombotic microangiopathy)
There have been reports of patients developing thrombotic microangiopathy generally within the first two weeks after Zolgensma treatment. Thrombotic microangiopathy is accompanied by a decrease in red blood cells and cells involved in clotting (platelets) and can be fatal. These blood clots could affect your child’s kidneys. Your child’s doctor may want to check your child’s blood (platelet counts) and blood pressure. Possible signs you need to look out for after your child is given Zolgensma include bruising easily, seizures (fits) or decrease in urine output (see section 4 for more information). Seek urgent medical attention if your child develops any of these signs.

Blood, organ, tissue and cell donation
After your child has been treated with Zolgensma, they 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 medicine such as prednisolone for about 2 months or longer (see also section 3) as part of Zolgensma treatment. The corticosteroid medicine will help manage any increase in liver enzymes that your child could develop after being given Zolgensma.

Vaccinations
As corticosteroids can affect the body’s immune (defence) system, your child’s doctor may decide to delay giving some vaccinations while your child is receiving corticosteroid treatment. Talk to your child’s doctor or nurse if you have any questions.

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

Additional information for parents/caregiver

Advanced SMA
Zolgensma can rescue living motor neurons, but does not rescue dead motor neurons. Children with less severe symptoms of SMA (such as absent reflexes or reduced muscle tone) may have sufficient living motor neurons to benefit significantly from Zolgensma treatment. Zolgensma may not work as well in children with severe muscle weakness or paralysis, breathing problems or who are not able to swallow, or in children who have significant malformations (such as heart defects), including patients with SMA Type 0, as there may be limited potential improvement after treatment with Zolgensma.
Your child’s doctor will decide if your child should be given this medicine.

Risk of tumours associated with potential insertion into the DNA
There is a possibility that therapies such as Zolgensma can insert into the DNA of human body cells.
As a consequence, Zolgensma could contribute to a risk of tumours because of the nature of the medicine. You should discuss this with your child’s doctor. In the event of a tumour, your child’s doctor may take a sample for further evaluation.

Hygiene care
The active substance in Zolgensma may temporarily be excreted through your child’s bodily waste;
this is called ‘shedding’. Parents and caregivers should follow good hand-hygiene for up to 1 month after your child is given Zolgensma. Wear protective gloves when coming into direct contact with your child’s bodily fluids or waste and wash hands thoroughly afterwards with soap and warm running water, or an alcohol-based hand sanitiser. Double bags should be used to dispose of soiled nappies and other waste. Disposable nappies may still be disposed of in household waste.

You should continue to 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.

Zolgensma will be given by a doctor or nurse trained in the management of your child’s condition.

The doctor will work out the amount of Zolgensma your child will receive according to your child’s weight. Zolgensma is given intravenously (into a vein) by a single infusion (drip) over about 1 hour.

Zolgensma will be given to your child ONCE only.

Your child will also be given prednisolone (or another corticosteroid) by mouth, starting 24 hours before being given Zolgensma. The dose of corticosteroid will also depend on your child’s weight.
Your child’s doctor will work out the total dose to give.

Your child will be given corticosteroid treatment daily for about 2 months after the dose of Zolgensma, or until your child’s liver enzymes decrease to an acceptable level. The doctor will slowly reduce the dose of corticosteroid until treatment can be fully stopped.

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

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

Seek urgent medical attention if your child develops any of the following serious side effects:

Common (may affect up to 1 in 10 people)
- bruising or bleeding for longer than usual if your child has been hurt – these may be signs of a low blood-platelet count.

Uncommon (may affect up to 1 in 100 people)
- vomiting, jaundice (yellowing of the skin or of the whites of the eyes) or reduced alertness - these may be signs of injury to the liver (including liver failure).
- bruising easily, seizures (fits), decrease in urine output – these may be signs of thrombotic microangiopathy.
- infusion-related reactions (see section 2, “Warnings and precautions”).

Rare (may affect up to 1 in 1 000 people)
- serious allergic reactions (see section 2, “Warnings and precautions”).

Talk to your child’s doctor or nurse if your child develops any other side effects. These can include:

Very common (may affect more than 1 in 10 people)
- increases in liver enzymes seen in blood tests.

Common (may affect up to 1 in 10 people):
- vomiting.
- fever.
- increases in troponin-I (a heart protein) seen in blood tests.

Reporting of side effects
If your child gets any side effects, talk to your child’s doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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

The following information is for healthcare professionals who will prepare and give 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 refers to the last day of that month.

Vials will be transported frozen (at or below -60ºC).

Upon receipt vials should be refrigerated at 2°C to 8°C immediately, and in the original carton.
Zolgensma therapy should be initiated within 14 days of receipt of vials.

This medicine contains genetically-modified organisms. Unused medicine or waste material must be disposed of in compliance with the local guidelines on handling of biological waste. As this medicine will be given by a doctor, the doctor is responsible for the correct disposal of the product. These measures will help protect the environment.

What Zolgensma contains
- The active substance is onasemnogene abeparvovec. Each vial contains onasemnogene abeparvovec with a nominal concentration of 2 × 1013 vector genomes/mL.
- The other ingredients are tromethamine, magnesium chloride, sodium chloride, poloxamer 188, hydrochloric acid (for pH adjustment) and water for injections.

What Zolgensma looks like and contents of the pack
Zolgensma is a clear to slightly opaque, colourless to faint white solution for infusion.

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

Each carton will contain between 2 to 14 vials.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestraße 10
6336 Langkampfen
Austria

Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11
Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111
Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf.: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 111

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00
Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888
France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01
Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50
Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1
Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

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The following information is intended for healthcare professionals only:

Important: Please refer to the Summary of Product Characteristics (SmPC) before using.

Each vial is for single use only.

This medicinal product contains genetically-modified organisms. Local guidelines on handling of biological waste should be followed.

Handling
- Zolgensma should be handled aseptically under sterile conditions.
- Personal protective equipment (including gloves, safety goggles, laboratory coat and sleeves) should be worn while handling or administering Zolgensma. Personnel should not work with Zolgensma if skin is cut or scratched.
- All spills of Zolgensma must be wiped with absorbent gauze pads and the spill area must be disinfected using a bleach solution followed by alcohol wipes. All clean-up materials must be double bagged and disposed of in accordance with local guidelines on handling of biological waste.
- All materials that may have come in contact with Zolgensma (e.g. vial, all materials used for injection, including sterile drapes and needles) must be disposed of in accordance with local guidelines on handling of biological waste.

Accidental exposure
Accidental exposure to Zolgensma must be avoided.

In case of accidental exposure to skin, the affected area must be thoroughly cleansed with soap and water for at least 15 minutes. In case of accidental exposure to eyes, the affected area must be thoroughly flushed with water for at least 15 minutes.

Storage
Vials will be transported frozen (at or below -60ºC). Upon receipt vials should be refrigerated at 2°C to 8°C immediately, and in the original carton. Zolgensma therapy should be initiated within 14 days of receipt of vials. The date of receipt should be marked on the original carton before the product is stored in the refrigerator.

Preparation
Vials should be thawed before use:
- For packs containing up to 9 vials – thaw for approximately 12 hours in the refrigerator (2ºC to 8ºC) or 4 hours at room temperature (20°C to 25°C).
- For packs containing up to 14 vials – thaw for approximately 16 hours in the refrigerator (2ºC to 8ºC) or 6 hours at room temperature (20°C to 25°C).

Do not use Zolgensma unless thawed.

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

After thawing, gently swirl Zolgensma. Do NOT shake.

Do not use this medicine if you notice any particles or discoloration once the frozen product has thawed and prior to administration.

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

Administration
Zolgensma should be given to patients ONCE only.

The dose of Zolgensma and exact number of vials required for each patient is calculated according to the patient’s weight (see SmPC sections 4.2 and 6.5).

To administer Zolgensma, draw the entire dose volume into the syringe. Once the dose volume is drawn into the syringe it must be administered within 8 hours. Remove any air in the syringe before administering to the patient via intravenous infusion through a venous catheter. Insertion of a secondary (‘back-up’) catheter is recommended in case of blockage in the primary catheter.

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

Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local guidelines on handling of biological waste.

Temporary Zolgensma shedding may occur, primarily through bodily waste. Caregivers and patient’s families should be advised on the following instructions for the proper handling of patients’ bodily fluids and waste:
- Good hand-hygiene (wearing protective gloves and washing hands thoroughly afterwards with soap and warm running water, or an alcohol-based hand sanitiser) is required when coming into direct contact with patient’s bodily fluids and waste for a minimum of 1 month after Zolgensma treatment.
- Disposable nappies should be sealed in double plastics bags and can be disposed of in household waste.