Strimvelis

Package leaflet: Information for the patient or user

Strimvelis 1-10 x 10^6 cells/mL dispersion for infusion

Autologous CD34-enriched cell fraction containing CD34 cells genetically modified with a retroviral vector containing the cDNA sequence encoding human adenosine deaminase (ADA)
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you observe in your child while he or she is receiving this medicine. See the end of section 4 for information on how to report adverse reactions.
Please read this leaflet carefully before this medicine is administered to your child, as it contains important information for your child.

• Keep this leaflet. You may need to read it again.
• If you would like more information or advice, please speak to your child’s doctor or nurse.
• If your child experiences any side effects, including those not listed in this leaflet, contact your child’s doctor or nurse. See section 4.
• Your child’s doctor will provide you with a patient alert card containing important safety information about your child’s treatment with Strimvelis. Please read it carefully and follow the instructions.
• Always carry the patient alert card and show it to the doctor or nurse whenever your child sees them, or if your child goes to hospital.

Contents of this package leaflet:

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

1. What Strimvelis is and what it is used for

Strimvelis is a type of medicine called gene therapy. It is specially manufactured for each individual patient.
Strimvelis is used in children to treat a serious condition called ADA-SCID
(severe combined immunodeficiency due to adenosine deaminase deficiency). It is used when your child
cannot receive a bone marrow transplant from a family donor due to insufficient compatibility.
ADA-SCID occurs due to a defective gene in the blood cells of your child's immune system. As a result, the cells do not produce sufficient amounts of an enzyme called adenosine deaminase (ADA), and your child's immune system does not function properly to defend the body against infections.
To produce Strimvelis, your child's bone marrow stem cells are modified in the laboratory to insert a gene that produces ADA. When these modified stem cells are returned to your child, they can divide and generate various types of blood cells, including the cells involved in your child's immune system.

2. What you should know before Strimvelis is administered to you (or your child)

Strimvelis is not suitable for some people
Strimvelis must not be given if your child:

• is allergic to any of the components of this medicine (listed in section 6).
• has or has had a type of cancer called leukaemia or myelodysplasia.
• has tested positive for HIV or certain other infections (your doctor will advise you on this).
• has previously received gene therapy.

Warnings and precautions
Information about cell-based medicines such as Strimvelis must be kept for 30 years at the hospital. The information that will be stored about your child includes their first name, last name, and the batch number of the Strimvelis received.
Strimvelis is specifically manufactured using the patient's own cells. It must never be given to anyone else.
Insertion of a new gene into the DNA may cause blood cancers. There has been one case of a blood cancer called leukaemia in a patient several years after treatment with Strimvelis. It is therefore important to monitor your child for symptoms of leukaemia. These include fever, shortness of breath, paleness, night sweats, fatigue, swollen lymph nodes, frequent infections, tendency to bleed and/or bruise easily, or red or purple spots under the skin. If your child develops any of these symptoms, you must contact the doctor immediately.
Before treatment with Strimvelis, your child will be given other medicines (see sections 3 and 4 for more information about these medicines, including possible side effects).
If your child has tested positive for hepatitis C, treatment may still be possible under certain conditions. Your doctor will discuss this with you if necessary.
Central venous catheters are thin, flexible tubes inserted by a doctor into a large vein to access your child’s bloodstream. Risks associated with these lines include infections and blood clots. The doctor and nurses will monitor your child for any complications related to the central venous catheter.
Treatment with Strimvelis has not been successful in some patients. These patients have received alternative treatment options.
There is a small risk of infection following treatment. Your child’s doctors and nurses will monitor for signs of infection during infusion and provide care if needed.
Some patients may develop autoimmunity, meaning an immune response against their own cells or tissues (see section 4). Your child’s doctor will discuss this with you if necessary.
After treatment, your child must never donate blood, organs, or tissues in the future. This is because Strimvelis is a gene therapy product.

When treatment with Strimvelis cannot be completed
In some cases, it may not be possible to proceed with the planned treatment with Strimvelis for the following reasons:

• a problem in collecting cells from your child’s bone marrow to produce the medicine.
• insufficient numbers of the correct type of cells in the tissue collected from your child’s body to produce the medicine.
• the medicine does not meet all quality control requirements.
• a delay in delivering the medicine to the hospital where your child’s treatment is taking place.

Before receiving Strimvelis, your child will be given chemotherapy to remove their existing bone marrow. If Strimvelis cannot be administered after chemotherapy, or if the modified stem cells do not engraft (take hold) in your child’s body, the doctor will administer replacement stem cells using the backup sample that was collected and stored before treatment began (see also section 3, How Strimvelis is administered).

You may need additional treatments
Strimvelis undergoes several quality checks before use. Because it is administered shortly after production, the final results of some of these tests may not be available before administration. If any test results indicate findings that could affect your child, the doctor will manage this appropriately.

Other medicines and Strimvelis
Tell your doctor if your child is taking, has recently taken, or might take any other medicines.
Your child must not receive vaccines known as live vaccines for 6 weeks before the conditioning treatment given prior to Strimvelis, or after treatment while your child’s immune system is recovering.

Strimvelis contains sodium
This medicine contains between 42 and 137 mg of sodium (a main component of cooking salt) per dose. This corresponds to 2–7% of the maximum daily dietary intake recommended for an adult.

3. How Strimvelis is administered

Strimvelis is administered by intravenous infusion (infusion) into a vein (intravenous route). It must be administered exclusively in a specialized hospital and by a physician experienced in treating patients with ADA-SCID and in the use of this type of medicine.
Before Strimvelis is prepared, the physician will perform tests to ensure that your child does not have certain infections (see section 2).
Two samples are taken
The physician will collect two bone marrow cell samples before the scheduled treatment:
the backup sample, collected at least 3 weeks before treatment with Strimvelis. This sample will be stored and may be administered as replacement cells if Strimvelis cannot be administered or is ineffective (see "When treatment with Strimvelis cannot be completed" in section 2)
the treatment sample, collected 4 or 5 days before treatment with Strimvelis. This sample will be used to prepare Strimvelis, by inserting a new gene into the cells.
Before and during treatment with Strimvelis

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The side effects associated with Strimvelis are all caused by the immune system becoming overactive and attacking the body's own tissues. Some side effects may be related to the medicine busulfan used to prepare your child’s bone marrow for treatment; these are marked with an asterisk (*) in the list below.

Very common: may affect more than 1 in 10 people:

• Runny or blocked nose ( allergic rhinitis )
• Shortness of breath, difficulty breathing ( asthma )
• Skin inflammation and itching ( atopic dermatitis, eczema )
• Elevated temperature ( pyrexia )
• Underactive thyroid ( hypothyroidism )
• High blood pressure ( hypertension )*
• Decrease in the number of red or white blood cells ( anemia, neutropenia )*
• Increased liver enzymes (indicating liver stress)*
• Blood test results positive for antinuclear antibodies and anti-smooth muscle antibodies (which may suggest possible autoimmunity)

Common: may affect up to 1 in 10 people:

• Red or purple spots on the skin, bleeding under the skin ( autoimmune thrombocytopenia )
• Inflammation of the thyroid ( autoimmune thyroiditis )
• Weakness and pain in the feet and hands due to nerve damage ( Guillain-Barré syndrome )
• Inflammation of the liver ( autoimmune hepatitis )
• Reduced number of blood cells ( autoimmune hemolytic anemia, autoimmune aplastic anemia )
• Blood test results positive for antineutrophil cytoplasmic antibodies (which may lead to autoimmune inflammation and swelling of blood vessels, and possibly increased risk of infections)
• A type of blood cancer called leukaemia

If you have any doubts about symptoms or side effects, or if any symptom concerns you, please consult your child’s doctor or nurse.

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, please consult your doctor or nurse. You may also report side effects directly through the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Strimvelis

The following information is intended for physicians only.
Keep this medicinal product out of the sight and reach of children.
Do not use this medicinal product after the expiry date and time stated on the container label and on the
infusion bag label.
Store refrigerated (2 °C–8 °C) for up to a maximum of 24 hours.
Keep the infusion bag inside the metal container until the time of administration. After removal from
refrigerated conditions, store at room temperature (15 °C–25 °C) for up to a maximum of 90 minutes and do
not re-refrigerate.
This medicinal product contains genetically modified human cells. Unused medicine and waste material must
be disposed of in accordance with local guidelines for handling materials of human origin. Since this
medicinal product will be administered by a qualified physician, the physician is responsible for the proper
disposal of the product. This will help protect the environment.

6. Package contents and other information

What Strimvelis contains

• The active substance is a cellular fraction enriched with autologous (patient's own) CD34 cells, genetically modified with a retroviral vector containing the cDNA sequence encoding human adenosine deaminase (ADA). The concentration is 1–10 x 10⁶ CD34 cells/mL.
• The other component is sodium chloride (see section 2, “Strimvelis contains sodium”).

Description of the appearance of Strimvelis and contents of the container
Strimvelis is a cellular dispersion for infusion, ranging from turbid to clear, colourless to pink, supplied in one or more infusion bags. The infusion bags are contained within a closed container.

Marketing Authorisation Holder
Fondazione Telethon ETS
Via Varese 16/B
00185 Rome
Italy

Manufacturer
AGC Biologics S.p.A.
Via Antonio Meucci 3
20091 Bresso
Italy

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.
This summary of product characteristics is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

The following information is intended exclusively for healthcare professionals:

Precautions to be taken before handling or administering the medicinal product
Healthcare professionals handling Strimvelis must take appropriate precautions (wear gloves, protective clothing, and eye protection) to avoid potential transmission of infectious diseases.
Strimvelis is transported directly to the healthcare facility where the infusion will be administered. The infusion bag(s) are placed in a sealed outer container. The bags must remain stored in the outer container until the time of use.
Strimvelis is for autologous use only. The patient's identity must be verified against the unique patient identification number on the infusion bag(s) and/or the outer container prior to infusion.
Gently agitate the infusion bag to redisperse any cellular aggregates, and administer using a transfusion administration set with a filter to remove any residual cellular aggregates.
Precautions for disposal of the medicinal product
Local guidelines for handling human-derived materials must be followed for unused medicinal product and associated waste. All materials that have come into contact with Strimvelis (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines for handling human-derived materials.
Accidental exposure
Avoid accidental exposure to Strimvelis. In the event of accidental exposure, local guidelines for handling human-derived materials should be followed, which may include washing contaminated skin and removing contaminated clothing. Work surfaces and materials that may have come into contact with Strimvelis must be decontaminated using appropriate disinfectants.