Strimvelis - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient or carer

Strimvelis 1–10 × 106 cells/mL dispersion for infusion

Autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence

This medicine is subject to additional monitoring. This will allow quick identification of new safety nformation. You canhelp by reporting any side effects your child may get. See the end of section 4 forhow to report side effects.

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

• – 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 gets any side effects, talk to your child’s doctor or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

• – Your child’s doctor will give you a Patient Alert Card which contains important safety information about your child’s treatment with Strimvelis. Read it carefully and follow the instructions on it.

• – Carry the Patient Alert Card with you at all times and always show it to the doctor or nurse when your child sees them or if your child goes to hospital.

What is in this leaflet

• 1. What Strimvelis is and what it is used for

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

• 3. How Strimvelis is given

• 4. Possible side effects

• 5. How to store Strimvelis

• 6. Contents of the pack and further information

1. What Strimvelis is and what it is used for

Strimvelis is a type of medicine called a gene therapy. It is made specially for each patient.

Strimvelis is used in children to treat a serious condition called ADA-SCID (adenosine deaminase-severe combined immune deficiency ). It is used when your child cannot receive a bone marrow transplant from a family donor because the match is not close enough.

ADA-SCID occurs because of a faulty gene in the blood cells of your child’s immune system. As a result, the cells do not produce enough of an enzyme called adenosine deaminase (ADA) and your child’s immune system does not work properly to defend the body against infections.

To make Strimvelis, stem cells from your child’s bone marrow are modified in the laboratory to insert a gene that produces ADA. When these modified stem cells are given back to your child, they can divide to produce different types of blood cells, including cells involved in your child’s immune system.

2. What you need to know before you (or your child) are given Strimvelis

Strimvelis is not suitable for some people

Strimvelis must not be given if your child:

• – is allergic to any of the ingredients 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 some other infections (your doctor will advise you about this)

• – has already been treated with gene therapy

Warnings and precautions

Information about cell-based medicinal products, like Strimvelis, must be kept for 30 years at the hospital. The information kept about your child will be your child’s name and the batch number of Strimvelis your child received.

Strimvelis is made specially from the patient’s own cells. It must never be given to anyone else.

Inserting a new gene into the DNA could cause blood cancer. There has been a case of blood cancer, called leukaemia in one patient several years after treatment with Strimvelis. It is therefore important to monitor your child for the symptoms of leukaemia.

These include fever, shortness of breath, paleness, night sweats, tiredness, swollen lymph glands, frequent infections, a tendency to bleed and/or bruise easily, or tiny red or purple spots under the skin. If your child develops any of these symptoms you should contact your doctor immediately.

Before treatment with Strimvelis, your child will be given other medicines (see sections 3 and 4 for more information on these medicines, including possible side effects).

If your child has previously tested positive for hepatitis C, your child can still be treated under certain conditions. Your doctor will discuss this with you if needed.

Central venous catheters are thin, flexible tubes, that are inserted by a doctor into a large vein to access the bloodstream of your child. The risks of these lines are infections and the formation of blood clots. The doctor and nurses will monitor your child for any central venous catheter complications.

Treatment with Strimvelis has been unsuccessful in some patients. These patients received alternative treatment options.

There is a small risk of infection as a result of the treatment. Your child’s doctors and nurses will monitor them throughout the infusion for signs of infection and provide treatment if needed.

Some patients can develop autoimmunity i.e. trigger an immune response against their own cells or tissues (see section 4). Your child’s doctor will discuss this with you if needed.

After the treatment, your child must not donate blood, organs, tissues or cells at any time in future. This is because Strimvelis is a gene therapy product.

When Strimvelis treatment cannot be completed

In some cases, it might not be possible to go ahead with the planned treatment with Strimvelis for reasons such as:

• a problem taking the cells from your child’s bone marrow to make the medicine
• not enough of the right type of cells in the tissue taken from your child’s body to make the medicine
• the medicine not meeting all the quality tests
• a delay in the medicine reaching the clinic where your child is being treated.

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

You may need other treatment

Strimvelis goes through a range of tests before it is used. Because it is given soon after it is made, the final results of some of these tests will not be ready before the medicine is given. If the tests show anything that might affect your child, the doctor will treat your child as appropriate.

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 be given vaccines called live vaccines for 6 weeks before they are given the conditioning medicine to prepare for Strimvelis treatment, nor after treatment while your child’s immune system is recovering.

Strimvelis contains sodium

This medicine contains 42 to 137 mg sodium (main component of cooking/table salt) in each dose. This is equivalent to 2 to 7% of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Strimvelis is given

Strimvelis is given by a drip (infusion) into a vein (intravenously). It must be given in a specialised hospital, and by a doctor who is experienced in treating patients with ADA-SCID and in using this type of medicine.

Before Strimvelis is made , the doctor will do tests to make sure that your child is not carrying certain infections (see section 2).

Two samples are collected

The doctor will collect two samples of bone marrow cells before the planned treatment:

• the backup sample, collected at least 3 weeks before Strimvelis treatment. It will be stored, to be given as replacement cells if Strimvelis cannot be given or does not work (see ‘When Strimvelis treatment cannot be completed’ in section 2)
• the treatment sample, collected 4 to 5 days before Strimvelis treatment. It will be used to make Strimvelis, by inserting a new gene into the cells.

Before and during Strimvelis treatment

4. Possible side effects

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

The side-effects linked to Strimvelis are caused by the immune system becoming over-active and attacking the body’s own tissues. Some side effects may also be related to the busulfan medicine 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)
• wheezing, difficulty breathing (asthma)
• inflamed itchy skin (atopic dermatitis, eczema)
• raised temperature (pyrexia)
• underactive thyroid gland (hypothyroidism)
• high blood pressure (hypertension)
• decreases in the number of red or white blood cells (anaemia, neutropenia)
• increases in liver enzymes (which indicate stress on the liver)
• blood test results positive for antinuclear antibody and smooth muscle antibody (which might suggest possible autoimmunity)

Common: may affect up to 1 in 10 people.

• red or purple dots on the skin, bleeding under the skin (autoimmune thrombocytopenia)
• inflamed thyroid gland (autoimmune thyroiditis)
• weakness and pain in the feet and hands caused by damage to nerves (Guillain-Barré syndrome)
• inflamed liver (autoimmune hepatitis)
• reduced numbers of blood cells (autoimmune haemolytic anaemia, autoimmune aplastic anaemia)
• blood test results positive for antineutrophil cytoplasmic antibody (which could lead to autoimmune inflammation and swelling of the blood vessels and possibly increased level of infections)
• a type of blood cancer called leukaemia

If you have any questions about symptoms or side effects, or if any symptoms concern you, talk to your child’s doctor or nurse.

Reporting of side effects

If your child gets 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 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 doctors only.

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

Do not use this medicine after the expiry date and time (EXP) which is stated on the container label and infusion bag label.

Store at 15–30 °C.

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

6. Contents of the pack and other information

What Strimvelis contains

• – The active substance is an autologous (the patient’s own) CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence. The concentration is 1–10 × 106 CD34+ cells/mL.

• – The other ingredient is sodium chloride (see section 2, “Strimvelis contains sodium”).

What Strimvelis looks like and contents of the pack

Strimvelis is a cloudy to clear, colourless to pink dispersion of cells for infusion, which is supplied in one or more infusion bags. The infusion bags are provided in a closed container.

Marketing Authorisation Holder

Orchard Therapeutics (Netherlands) BV

Prins Bernhardplein 200,

1097 JB Amsterdam,

the Netherlands

Manufacturer

AGC Biologics S.p.A.

58 Via Olgettina

20132

Milan

ITALY

This leaflet was last revised in MM/YYYY.

Other sources of information

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

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only:

Precautions to be taken when handling or administering the medicinal product

Healthcare professionals handling Strimvelis should take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases.

Strimvelis is transported directly to the medical facility where the infusion will be administered. The infusion bag(s) is/are placed inside a closed outer container. The bags must be kept in the outer container until ready to use.

Strimvelis is intended solely for autologous use. The identity of the patient must be matched with the essential unique patient information on the primary and/or outer container prior to infusion.

Gently agitate the infusion bag to re-disperse any cellular aggregates, administer using a transfusion administration set with filter to remove any remaining cellular aggregates.

Precautions to be taken for the disposal of the medicinal product

Local guidelines on handling human-derived material should be followed for unused medicinal product or waste material. All material that has been in contact with Strimvelis (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling human-derived material.

Accidental exposure

Accidental exposure to Strimvelis must be avoided. Local guidelines on handling of human derived materials should be followed in case of accidental exposure, which may include washing of the contaminated skin and removal of contaminated clothes. Work surfaces and materials which have potentially been in contact with Strimvelis must be decontaminated with appropriate disinfectant.

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