Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - casgevy

Document Subject

Generated Narrative: MedicinalProductDefinition mp7231462c5958bc15b9c9fab8da21ba25

identifier: http://ema.europa.eu/identifier/EU/1/23/1787/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Casgevy 4 - 13 × 106 cells/mL dispersion for infusion

type: Full name

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part: nan

type: Invented name part

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part: nan

type: Scientific name part

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part: nan

type: Strength part

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type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-7231462c5958bc15b9c9fab8da21ba25

identifier: http://ema.europa.eu/identifier/EU/1/23/1787/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - casgevy

Attesters

What is in this leaflet

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 given to you
4. Possible side effects
5. How to store Casgevy
6. Contents of the pack and other information

What Casgevy is Casgevy is a gene therapy product that contains the active substance exagamglogene autotemcel.

Casgevy is made specifically for you using your own blood stem cells. Blood stem cells can turn into other blood cells including red blood cells, white blood cells, and blood platelets. These cells are collected from your blood, then genetically modified and given back to you as a transplant in a hospital.

What Casgevy is used for Casgevy is used to treat:

• People aged 12 years and older with beta-thalassemia who need regular blood transfusions (transfusion-dependent thalassemia, TDT). People with TDT do not make enough haemoglobin, a protein in the blood that carries oxygen through the body, due to a gene defect. This causes anaemia, and they need regular blood transfusions.
• People aged 12 years and older with sickle cell disease (SCD) who have frequent painful crises (called vaso-occlusive crises or VOCs). Patients with SCD have a different form of haemoglobin (sickle cell haemoglobin or HbS) from other people due to a gene defect. HbS leads to abnormal sickle-shaped red blood cells that stick together and cannot easily move through blood vessels. This can lead to the blockage of blood vessels, causing VOCs.

How Casgevy works Casgevy works by increasing the production of a special type of haemoglobin called Haemoglobin F (foetal haemoglobin or HbF). Having more HbF improves the production and function of red blood cells. Because of this, people with TDT may not need blood transfusions and people with sickle cell disease may not experience VOCs.

You must not be given Casgevy:

• 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 medicines you will be given to prepare you for treatment with Casgevy (see section 3).

Tell your doctor straight away if either of these applies to you or if you are not sure. The treatment will not be given to you if you are allergic to any of these medicines.

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

Before treatment with Casgevy:

• You will have two other types of medicines before you are given Casgevy. For more information on these medicines, see section 3.* Mobilisation medicine(s) to move the blood stem cells from your bone marrow into the blood stream so they can be collected to make Casgevy. This step will take 2-6 days. * Conditioning medicine is given to you shortly before you are given Casgevy. This creates space in the bone marrow for new blood cells to grow following treatment with Casgevy.
• The doctor will discuss the possible impact of the conditioning medicine on fertility. See below under Fertility in men and women .
• In people with SCD, it can be more difficult to move the blood stem cells from the bone marrow and therefore to collect them, compared to people with TDT. More mobilisations and collections may therefore be needed in people with SCD than people with TDT.

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 help the blood to clot). Low levels of platelets 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 neutrophils (a type of white blood cell that usually prevents infections). Low levels of neutrophils 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 other signs of infections such as sore throat, cough or shortness of breath, pain or burning when urinating or urinating often, or diarrhoea.

• Your doctor will monitor blood cell levels and give you treatment as required. The doctor will tell you when your platelets and neutrophils return to safe levels.

• The doctor will monitor your blood cell levels and overall health to help researchers understand the long-term effects of Casgevy.

• In some patients, haemoglobin levels may be lower than is normally expected for their age and sex.

• After treatment with Casgevy there is a theoretical risk of blood cancers (myelodysplasia, leukaemia, or lymphoma), although this has not been seen in studies with Casgevy. Your doctor will monitor you at least once a year for 15 years for any signs of blood cancers.

• Ingredients of Casgevy called dimethyl sulfoxide (DMSO), dextran 40 and Cas9 may cause serious allergic reactions. Your doctor or nurse will monitor you for signs and symptoms of an allergic reaction both during and after treatment with Casgevy. See also section 2 Casgevy contains sodium and dimethyl sulfoxide (DMSO).

• Casgevy is tested for the presence of infectious microbes, but a small risk of infection remains. Your doctor or nurse will monitor you for signs and symptoms of infections and provide treatment as needed.

• After treatment with Casgevy, you must not donate blood, organs, tissues, or cells.

• 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 treatment cannot be completed or fails 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 give you an injection into a vein that contains your rescue cells (your own original and untreated blood stem 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 TDT or SCD.

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

Other medicines and Casgevy 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 such as dexteroxamine, deferiprone and/or deferasirox) 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 you if and when you should start taking these medicines after Casgevy treatment.

Vaccines called live vaccines must not be given for 6 weeks before the conditioning medicine used to prepare for Casgevy treatment, nor after treatment while your immune system (the body s defence system) is recovering. Talk to your doctor if you need to have any vaccinations.

Pregnancy This treatment must not 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 treatment 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 discuss with you the benefit of breast-feeding for your baby versus potential risks of 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.

Driving and using machines 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.

Casgevy contains sodium and dimethyl sulfoxide (DMSO) 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.

This medicine contains approximately 50 mg DMSO per mL. See Section 2 Warnings and precautions .

Casgevy is given only once.

Casgevy can only be given in an authorised treatment centre (specialised hospital) by doctors with experience in stem cell transplants, and in the treatment of patients with blood disorders such as TDT and SCD.

STEP 1: Before Casgevy treatment, a doctor will give you a mobilisation medicine. This medicine moves blood stem cells from your bone marrow into the blood stream. The cells are then collected in a machine that separates the different blood cells (this is called apheresis). The entire step may happen more than once. Each collection step takes about one week.

Rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated in case there is a problem in the treatment process. See above in section 2, If Casgevy treatment cannot be completed or fails .

STEP 2: Your blood stem cells will be sent to the manufacturing site where they are used to make Casgevy. It may take up to 6 months from the time your cells are collected to manufacture and test Casgevy before it is sent back to your doctor.

STEP 3: Shortly before your stem cell transplant, the doctor will give you a conditioning medicine in the hospital. This step takes about 2 to 6 days and will prepare you for treatment by removing cells from the bone marrow, so they can be replaced with the modified cells in Casgevy. After you are given this medicine, the number of blood cells will fall to very low levels (see section 4). You will stay in the hospital at this point until after the Casgevy infusion.

STEP 4: One or more vials of Casgevy will be given as an injection into a vein through a central venous catheter. Central venous catheters are thin, flexible tubes, that are inserted by a doctor into a large vein to access your bloodstream. The risks of catheters are infections and the formation of blood clots. The doctor and nurses will monitor you for any central venous catheter complications. It may take a few hours for all of the injections to be given. After you are given Casgevy, you will stay in hospital so that your healthcare team can closely monitor your recovery. This can take approximately 2 months, but times can vary. A doctor will decide when you can go home.

Like all medicines, this medicine can cause side effects, although not everybody gets them. Talk to your doctor or nurse about possible side effects.

Some side effects are related to the mobilisation medicine and the conditioning medicine. You should also read the package leaflets for these medicines.

The following serious side effects can happen within the first few days or weeks after treatment but can also develop much later.

• Pain in the right upper abdomen under the ribs, yellowing of eyes or skin, rapid weight gain, swelling of arms, legs and abdomen, and trouble breathing. These may be signs of a serious liver condition called veno-occlusive disease.
• 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. These may be signs of thrombocytopenia, low levels of platelet cells, which can reduce the ability of blood to clot and may lead to bleeding.
• Fever, chills or infections. These may be signs of neutropenia, low levels of white bloods cells called neutrophils that fight infections.

Tell your doctor immediately if you get any of the side effects listed above.

Other side effects occurring with the mobilisation medicine and cell collection

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

• feeling sick (nausea)
• vomiting
• headache
• belly pain
• muscle or bone pain

Common (may affect up to 1 in 10 people)

• lung condition with symptoms of sudden chest pain, fever, difficulty breathing, and signs of fluid collection in the lungs on a chest x-ray which occurs in sickle cell disease (acute chest syndrome)
• painful sickle cell crisis (sickle cell anaemia with crisis)
• fever
• high levels of white blood cells (leukocytosis)
• diarrhoea
• mouth and throat pain
• numbness in the mouth
• joint pain
• general pain
• feeling tired
• low blood potassium levels (hypokalaemia)
• low blood magnesium levels (hypomagnesaemia)
• high blood phosphate levels (hyperphosphataemia)

Other side effects occurring with the conditioning medicine

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

• fever during a period of low neutrophil (a type of white blood cell) counts (febrile neutropenia)
• low levels of red blood cells (anaemia)
• low levels of lymphocytes, a type of white blood cell (lymphopenia)
• low levels of white blood cells (leukopenia)
• low blood potassium levels (hypokalaemia)
• high blood phosphate levels (hyperphosphataemia)
• low blood magnesium levels (hypomagnesaemia)
• low blood phosphate levels (hypophosphataemia)
• fluid retention
• headache
• fever
• feeling tired
• nosebleed
• feeling sick (nausea)
• vomiting
• belly pain
• inflammation of the stomach lining
• constipation
• diarrhoea
• mouth and throat pain
• inflammation of mucous membranes, such as gums (mucositis)
• decreased appetite
• weight loss
• muscle or bone pain
• dry skin
• flaky skin
• discolouring of the skin and nails
• tiny blood spots under the skin
• rash
• hair loss (alopecia)
• high blood levels of bilirubin, a breakdown product of red blood cells, which can cause yellowing of the skin and eyes (hyperbilirubinaemia)
• increased blood levels of a liver enzyme (alanine aminotransferase)

Common (may affect up to 1 in 10 people)

• set of pneumonia-like symptoms, such as fever, chills, coughing, and breathing problems, that occur with no sign of infection in the lung (idiopathic pneumonia syndrome)
• inability of the lungs to add oxygen to your blood (respiratory failure)
• difficulty breathing
• infection in the blood (sepsis)
• infection in the blood cause by the bacteria Klebsiella (Klebsiella sepsis)
• infection of the lung (pneumonia)
• infection of the mouth cause by a fungus (oral candidiasis)
• infection of hair follicles (folliculitis)
• increased heart rate (tachycardia)
• increased blood levels of liver enzymes (aspartate aminotransferase, gamma- glutamyltransferase)
• low blood pressure (hypotension)
• low oxygen levels in the blood (hypoxia)
• enlarged liver
• enlarged spleen
• nerve damage in arms and/or legs causing pain or numbness, burning and tingling (peripheral neuropathy)
• problems with the nerves that cause pain or numbness, burning and tingling sensation (peripheral sensory neuropathy)
• nerve pain
• problems with sense of taste
• blurred vision
• dry eyes
• hot flushes
• cough
• indigestion
• disease where stomach acid rises up above the stomach into the oesophagus or food pipe (gastroesophageal reflux disease)
• gum bleeding (gingival bleeding)
• sore throat
• trouble swallowing
• inflammation in the large bowel, causing pain and diarrhoea (colitis)
• inflammation of the food pipe (oesophagitis)
• blood in vomit
• rectal bleeding
• inflammation of the stomach and gut
• mouth ulcers
• general pain
• painful urination
• blood in urine
• missed menstruation
• bleeding between menstruation periods
• bleeding between menstrual periods
• irregular menstruation
• pain in the vulva and vagina
• early menopause
• weight gain
• bruising
• itching
• reddening of the skin
• cuts or scrapes of the skin
• low levels of all types of blood cells (pancytopenia)
• low levels of reticulocytes, a type of immature red blood cell (reticulocytopenia)
• bleeding in an area of the brain involved in balance and coordination (cerebellar haemorrhage)
• abnormal build-up of fluid that surrounds the brain and the spinal cord (hydrocephalus)
• low levels of albumin, a blood protein (hypoalbuminaemia)
• low blood calcium levels (hypocalcaemia)
• joint pain
• longer time for your blood to clot
• higher level of an indicator of inflammation (C-reactive protein)
• longer time for the transplanted cells to start growing and producing normal blood cells (delayed engraftment) Other side effects occurring with Casgevy

Common (may affect up to 1 in 10 people)

• immune system disorder (haemophagocytic lymphohistiocytosis) where types of white blood cells (histiocytes and lymphocytes) build up in organs, causing excess inflammation and tissue destruction. Symptoms may include a fever that is not due to infection and does not respond to antibiotics, an enlarged liver and/or spleen, skin rash, breathing problems, bruising easily, low blood pressure, 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 (acute respiratory distress syndrome)
• set of pneumonia-like symptoms, such as fever, chills, coughing, and breathing problems, that occur with no sign of infection in the lung (idiopathic pneumonia syndrome)
• increased heart rate (tachycardia)
• low levels of red blood cells (anaemia)
• low levels of white blood cells (leukopenia)
• low blood calcium levels (hypocalcaemia)
• headache
• sensations like numbness, tingling, pins and needles (paraesthesia)
• nosebleed
• rash
• tiny blood spots under the skin
• fever
• chills
• longer time for the transplanted cells to start growing and producing normal blood cells (delayed engraftment)
• events such as chills and increased heart rate at the time you are given Casgevy (infusion related reactions)

Tell your doctor or nurse if you experience any of these side effects. Tell your doctor or nurse right away if any of these side effects get worse.

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.

This information is intended for doctors and nurses only.

As this medicine will be given by a qualified doctor or nurse, they are responsible for the correct storage of the medicine before and during its use, as well as for its correct disposal.

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

Do not use this medicine after the expiry date which is stated on the carton and on each vial.

Store frozen, at or below -135 C for up to two years. Keep the vial(s) in the carton until ready to thaw. Thaw one vial at a time. Do not thaw until ready to infuse. Do not re-freeze after thawing. Once thawed, store at room temperature (20 C to 25 C) and infuse within 20 minutes. This medicine contains human blood cells. Unused medicine must be disposed of in compliance with the local guidelines on handling human-derived material.

What Casgevy contains

• The active substance is exagamglogene autotemcel. Each mL of Casgevy contains 4-13 106 CD34+ 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 What you need to know before you are given Casgevy .

What Casgevy looks like and contents of the pack

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. The number of vials is specific to each patient s dose. 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.

Marketing Authorisation Holder and Manufacturer

Vertex Pharmaceuticals (Ireland) Limited
Unit 49, Block F2, Northwood Court, Santry,
Dublin 9, D09 T665,
Ireland
Tel: +353 (0)1 761 7For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien, , esk
republika, Danmark, Deutschland, Eesti, France, Hrvatska, Ireland, sland, , Latvija, Lietuva, Luxembourg/Luxemburg, Magyarorsz g, Malta, Nederland, Norge, sterreich, Polska, Portugal, Rom nia, Slovenija, Slovensk republika, Suomi/Finland, Sverige, United Kingdom (Northern Ireland) Vertex Pharmaceuticals (Ireland) Limited T l/Tel/Te /Tlf/S mi/ /Puh:
+353 (0) 1 761 7Espa a Vertex Pharmaceuticals Spain, S.L. Tel: + 34 91 7892
Vertex

: +30 (211) 2120Italia Vertex Pharmaceuticals (Italy) S.r.l. Tel: +39 0697794This leaflet was last revised in

This medicine has been given conditional approval . This means that there is more evidence to come about this medicine. The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: