Casgevy 4-13 x 10Exp6 cells/mL dispersion for infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

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

Casgevy is a cell therapy, which is given to you once only as a blood stem cell transplant. It is made from your own blood stem cells and is made specifically for you. Blood stem cells can turn into other blood cells including red cells, white cells and platelets. Cells are taken from you, then are modified and given back to you as a transplant in a hospital.

Casgevy is used to treat:

• People aged 12 years and older with beta-thalassemia who need regular blood transfusions. People with beta-thalassemia do not have enough haemoglobin, a protein in the blood that carries oxygen throughout the body. This causes anaemia, and they need regular blood transfusions.
• People aged 12 years and older with sickle cell disease who have frequent painful crises (called vaso-occlusive crises). Patients with sickle cell disease have a different form of haemoglobin from other people (sickle cell haemoglobin). It produces abnormal sickle-shaped red blood cells, and these can lead to the blockage of blood vessels, causing vaso-occlusive crises.

Casgevy works by increasing the production of a special type of haemoglobin called Haemoglobin F (foetal haemoglobin). Having more Haemoglobin F increases haemoglobin levels in the body and improves the production and function of red blood cells. This can mean that people with beta-thalassemia may not need blood transfusions. For people with sickle cell disease, it can also reduce or even stop their vaso-occlusive crises.

• if you are allergic to exagamglogene autotemcel or any of the other ingredients in this medicine (listed in section 6).
• If you are allergic to any of the ingredients in the mobilisation or conditioning medicines you will be given before treatment with Casgevy (see section 3).

Tell your doctor straight away if either of these applies to you. The treatment will not be given to you.

Talk to your doctor or nurse before you are given Casgevy.

Before treatment with Casgevy:

• You will have two other types of medicine before you are given Casgevy. For more information on these medicines, see section 3.
  • Mobilisation medicine that moves the blood stem cells into the blood stream, allowing them to be collected to make Casgevy. This will take 2-6 days.
  • Conditioning medicine to clear cells from the bone marrow, shortly before you are given Casgevy.
• The doctor will discuss the possible impact of the conditioning medicine on fertility. See below under “Fertility in men and women”.

After treatment with Casgevy:

• You will have fewer blood cells for a while, until Casgevy takes hold in your bone marrow. This includes:
  • Low levels of platelets, cells that usually help the blood to clot. Low levels may cause bleeding.
    Tell your doctor right away if you have any of these signs of low platelet cell levels: severe headache, abnormal bruising, prolonged bleeding, or bleeding without injury such as nosebleeds, bleeding from gums, blood in your urine, stool, or vomit, or coughing up blood.
  • Low levels of white blood cells that usually prevent infections. Low levels may make infections more likely.
    Tell your doctor right away if you have any of these signs of low white blood cell levels: fever, chills, or infections.
• Your doctor will monitor blood cell levels and give you treatment as required. The doctor will tell you when they return to safe levels.
• You must not donate blood, organs, tissues or cells.
• The doctor will monitor your blood cell levels and overall health to help understand the long-term effects of Casgevy.

Casgevy is made from your own cells and is only given to you. Information about cell-based medicinal products must be kept for 30 years at the hospital where you receive the treatment. The information they keep will include your name, name of the product and the batch number(s) of Casgevy you received.

If Casgevy cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold in the body, the doctor may decide to return your own original blood stem cells (rescue cells) that are collected and stored before treatment starts (see section 3). If you are given rescue cells, you will not have any treatment benefit and will still need treatment for either beta-thalassemia or sickle cell disease.

Casgevy is not to be given to children under 12. It is not yet known if Casgevy is safe and effective in these children.

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

Do not take medicines that remove iron from your body (chelating agents) for at least 7 days before you are given the conditioning medicine. Your doctor will advise you if and when you can start taking these medicines after Casgevy treatment.

Do not take other medicines for sickle cell disease (such as hydroxyurea/hydroxycarbamide, crizanlizumab or voxelotor) for at least 8 weeks before you are given the mobilisation and conditioning medicines. Your doctor will advise if and when you should start taking these medicines after Casgevy treatment.

Talk to your doctor if you need to have any vaccinations.

• Pregnancy
  This treatment is not to be given during pregnancy because of the possible effects of the conditioning medicine. The effects of Casgevy in pregnant women are not known. Talk to your doctor about pregnancy after receiving Casgevy.
  If you are pregnant or think you may be pregnant after treatment with Casgevy, talk to your doctor immediately.
  If you are a woman who can get pregnant, you will be given a pregnancy test before starting mobilisation and conditioning medicines to make sure you are not pregnant.
• Contraception in men and women
  If you are a woman who can get pregnant, or a man capable of fathering a child, you must use an effective method of contraception from the start of mobilisation and for at least 6 months after receiving Casgevy. Talk to your doctor about which methods of contraception are appropriate.
• Breast-feeding
  Breast-feeding must be stopped during conditioning because of the possible effects of the conditioning medicine. It is not known whether the ingredients of Casgevy can pass into breast milk. Your doctor will consider the benefit of breast-feeding for your baby and the benefit of treatment for you to help you decide whether you can breast-feed after Casgevy treatment.
• Fertility in men and women
  It may not be possible for you to become pregnant or father a child after you have had the conditioning medicine. You should discuss your options with your doctor before treatment. These may include storing reproductive material (for instance, eggs, sperm) to use at a later time.

The mobilisation medicine and conditioning medicines used before Casgevy treatment may cause dizziness and fatigue. If you feel dizzy, tired, or unwell, do not drive, use machines or take part in activities that need you to be alert.

This medicine contains approximately 5.3-70 mg sodium (main component of table salt) per vial. This is equivalent to 0.3-4% of the recommended maximum daily dietary intake of sodium for an adult. The total number of vials comprising a dose varies per patient.

DMSO and dextran 40 are substances used to preserve frozen cells. If you have not previously come into contact with them, the medical team will monitor you closely for any allergic reactions during and after the infusion of Casgevy.

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

• lower levels of white blood cells, sometimes with a fever, which may make you more susceptible to infection
• lower levels of red blood cells
• increased liver enzymes (signs of stress on the liver)
• yellow discolouration of the eyes and skin (jaundice), caused by high levels of bilirubin in the blood
• changes in levels of potassium, phosphate and magnesium in your blood
• fever
• headache
• mouth pain
• nosebleed
• inflamed mucous membranes (e.g., gums)
• inflammation of the stomach or colon
• stomach pain
• nausea
• vomiting
• diarrhoea
• constipation
• decreased appetite
• weight loss
• swelling in the face, hands and feet caused by excess fluid
• pain in bones or muscles
• sunspots, freckles or red dots on the skin
• dry or flaky skin
• rash
• hair loss
• feeling tired or weak

Common side effects (may affect up to 1 in 10 people)

• inflammation caused by the immune system making too many infection fighting cells (haemophagocytic lymphohistiocytosis) - symptoms may include enlarged liver and/or spleen, skin rash, breathing problems, easy bruising, kidney abnormalities, and heart problems
• difficulty breathing, which could require oxygen to help you breathe, sometimes with pain in the chest, fever, chills or coughing
• multiple symptoms such as fever, skin rash, diarrhoea or unexplained weight gain occurring at the same time, usually in the first month after treatment (engraftment syndrome)
• increased time for blood to clot
• infections
• enlarged spleen or liver
• increased heart rate
• decreased blood pressure
• changes in levels of calcium in your blood
• low oxygen levels in the blood
• irregular blood clotting
• chills
• problem with nerves, causing pain, numbness or tingling
• tingling or prickling sensation
• blurred vision
• cough
• sore throat
• trouble swallowing
• indigestion
• bruising or reddening of the skin
• cuts or scrapes of the skin
• itchy skin
• joint pain or general pain
• menstruation changes such as missed menstruation, bleeding between menstruation periods, irregular menstruation, vaginal pain, pain during menstruation, and early menopause.
• difficulty or discomfort when urinating
• weight gain
• dry eyes
• hot flushes

Tell your doctor or nurse right away if side effects become severe.

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:

or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is exagamglogene autotemcel. Each mL of Casgevy contains 4-13 × 10⁶ cells (blood stem cells).
• The other ingredients are a solution used to preserve frozen cells, which contains sodium, dimethyl sulfoxide (DMSO) and dextran 40. See section 2.

Casgevy is a semi-transparent dispersion for infusion. Casgevy is supplied in vials containing 1.5 mL to 20 mL. One or more vials are packed in a carton. One carton may contain up to 9 vials. Your dose may consist of multiple vials and cartons.

Your name and date of birth, as well as coded information identifying you as the intended recipient are printed onto each carton and vial.

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