Casgevy

Patient Information Leaflet

Casgevy 4 - 13 × 10 cells/mL infusion dispersion

exagamglogene autotemcel (CD34 cells)
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 experience while receiving this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before receiving this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Casgevy is and what it is used for

What Casgevy is
Casgevy is a gene therapy medicine that contains the active substance exagamglogene autotemcel.
Casgevy is specifically manufactured for you using your own blood stem cells.
Blood stem cells can develop into other types of blood cells, including red blood cells, white blood cells, and platelets. These cells are collected from your blood, then genetically modified and reinfused into your body as a transplant in a hospital setting.

What Casgevy is used for
Casgevy is used to treat:

• People aged 12 years and older with beta-thalassemia who require regular blood transfusions (transfusion-dependent thalassemia). People with transfusion-dependent thalassemia do not produce sufficient amounts of haemoglobin, a protein in the blood that carries oxygen throughout the body, due to a genetic defect. This causes anaemia, and such individuals require regular blood transfusions.
• People aged 12 years and older with sickle cell disease who experience frequent painful crises (called vaso-occlusive crises). Patients with sickle cell disease have a different form of haemoglobin (sickle haemoglobin or HbS) due to a genetic defect. HbS causes red blood cells to become abnormal and sickle-shaped, which stick together and cannot move easily through blood vessels. This can block blood vessels, leading to vaso-occlusive crises.

How Casgevy works
Casgevy works by increasing the production of a particular type of haemoglobin called fetal haemoglobin (HbF). Increased levels of HbF improve the production and function of red blood cells. As a result, people with transfusion-dependent thalassemia may no longer require blood transfusions, and people with sickle cell disease may stop experiencing vaso-occlusive crises.

2. What you need to know before receiving Casgevy

Do not receive Casgevy:

• if you are allergic to exagamglogene autotemcel or to any of the other components of this medicine (listed in section 6);
• if you are allergic to any of the components of the medicines you will receive to prepare you for treatment with Casgevy (see section 3).

Inform your doctor immediately if any of these situations apply to you or if you have any doubts. Treatment
will not be administered if you are allergic to any of these medicines.
Warnings and precautions
Talk to your doctor or nurse before receiving Casgevy.
Before treatment with Casgevy

• You will receive two other types of medicines before Casgevy is administered. For more information about these medicines, see section 3. o Medicine(s) for mobilisation, to move blood stem cells from the bone marrow into the bloodstream so they can be collected for the production of Casgevy. This procedure will take 2–6 days. o The conditioning medicine is given shortly before you receive Casgevy. This creates space in the bone marrow so that new blood cells can grow after treatment with Casgevy.
• Your doctor will discuss the possible effects of the conditioning medicine on fertility. See below “Fertility in men and women”.
• In people with sickle cell disease, it may be more difficult to move blood stem cells from the bone marrow and therefore collect them, compared to people with transfusion-dependent thalassaemia. Therefore, people with sickle cell disease may require more cycles of mobilisation and collection than people with transfusion-dependent thalassaemia.

After treatment with Casgevy

• You will have lower blood cell counts for a certain period, until Casgevy engrafts in the bone marrow. This includes: o Low platelet levels (cells that help blood to clot): low platelet levels can cause bleeding. Inform your doctor immediately if you have any of the following signs of low platelet levels: severe headache, unusual bruising, prolonged bleeding, or bleeding without injury, such as nosebleeds, bleeding gums, blood in urine, stools or vomit, or coughing up blood.

o Low neutrophil levels (a type of white blood cell that normally prevents infections):
low neutrophil levels can increase the risk of infection.
Inform your doctor immediately if you have any of the following signs of low white blood cell levels: fever, chills or other signs of infection, such as sore throat, cough or shortness of breath, pain or burning when urinating, increased frequency of urination, or diarrhoea.

• Your doctor will monitor your blood cell levels and prescribe treatment if necessary. Your doctor will inform you when platelet and neutrophil levels return to safe levels.
• Your doctor will monitor your blood cell levels and your general health to help researchers understand the long-term effects of Casgevy.
• In some patients, haemoglobin levels may be lower than normally expected based on age and sex.
• There is a theoretical risk of blood cancers (myelodysplasia, leukaemia or lymphoma) after treatment with Casgevy, although this has not been observed in clinical studies with Casgevy. Your doctor will perform checks at least once a year for 15 years to detect any signs of blood cancers.
• Components of Casgevy called dimethyl sulfoxide (DMSO), dextran 40 and Cas9 may cause severe 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 microorganisms, but a small risk of infection remains. Your doctor or nurse will monitor you for signs and symptoms of infections and provide treatment if necessary.
• After treatment with Casgevy, you must not donate blood, organs, tissues or cells.
• Casgevy is manufactured using your own cells and is administered only to you. Information on cell-based medicines must be kept for 30 years at the hospital where you received treatment. The information stored will include your name, the name of the medicine, and the batch number(s) of Casgevy you received.

If treatment with Casgevy cannot be completed or fails
If Casgevy cannot be administered after the conditioning medicine, or if the modified blood stem cells do not engraft in your body, your doctor may decide to administer an intravenous infusion containing your backup cells (your original, untreated blood stem cells) that were collected and stored before starting treatment (see section 3). If you receive the backup cells, you will not receive any benefit from treatment and will continue to require treatment for transfusion-dependent thalassaemia or sickle cell disease.
Children under 12 years of age
Casgevy must not be given to children under 12 years of age. It is not yet known whether 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 the body (chelating agents, such as deferoxamine,
deferiprone and/or deferasirox) for at least 7 days before receiving the conditioning medicine. Your doctor will inform you if and when you can start taking these medicines again after treatment with Casgevy.
Do not take other medicines for sickle cell disease (e.g., hydroxycarbamide/hydroxyurea,
crizanlizumab or voxelotor) for at least 8 weeks before receiving the mobilisation and conditioning medicines. Your doctor will inform you if and when you should start taking these medicines after treatment with Casgevy.
Live vaccines must not be administered within 6 weeks before the conditioning medicine used to prepare you for treatment with Casgevy, or after treatment while your immune system (your body’s defences) is recovering.
Consult your doctor if you need vaccinations.
Pregnancy
This treatment must not be given during pregnancy due to the possible effects of the conditioning medicine. The effects of Casgevy in pregnant women are not known. Consult your doctor regarding pregnancy after receiving Casgevy.
If you are pregnant or suspect you may be pregnant after treatment with Casgevy, contact your doctor immediately.
If you are a woman of childbearing potential, you will undergo a pregnancy test before starting the mobilisation and conditioning medicines to rule out pregnancy.
Contraception in men and women
If you are a woman of childbearing potential or a man capable of fathering children, you must use an effective method of contraception from the start of mobilisation treatment and for at least 6 months after receiving Casgevy. Consult your doctor about appropriate contraceptive methods.
Breast-feeding
Breast-feeding must be stopped during conditioning due to the possible effects of the conditioning medicine. It is not known whether components of Casgevy can pass into breast milk. Your doctor will discuss with you the benefit of breast-feeding for your baby versus the potential risks of treatment.
Fertility in men and women
You may be unable to become pregnant or father a child after receiving the conditioning medicine. You should discuss available options with your doctor before treatment. These may include preserving reproductive material (e.g., eggs, sperm) for use at a later time.
Driving and using machines
The medicine for mobilisation and the conditioning medicines used before treatment with Casgevy may cause dizziness and fatigue. If you experience dizziness, fatigue or feeling unwell, do not drive, operate machinery or perform activities requiring alertness.
Casgevy contains sodium and dimethyl sulfoxide (DMSO)
This medicine contains approximately 5.3–70 mg of sodium (a key component of table salt) per vial. This corresponds to 0.3–4% of the maximum daily recommended dietary intake for an adult. The total number of vials that make up a dose varies depending on the patient.
This medicine contains approximately 50 mg of DMSO per mL. See section 2 “Warnings and precautions”.

3. How Casgevy is produced and administered

Casgevy is administered as a single dose.
Casgevy can only be administered at an authorized treatment center (a specialized hospital)
by physicians experienced in stem cell transplantation and the management of patients with
hematological disorders, such as transfusion-dependent thalassemia and sickle cell disease.

PHASE 1: Prior to treatment with Casgevy, your doctor will give you a mobilization medicine.
This medicine moves blood stem cells from the bone marrow into the bloodstream. The cells are then
collected using a machine that separates the different blood cells (this procedure is called apheresis).
This entire phase may be repeated more than once. Each cell collection phase takes approximately one week.

Additionally, “rescue cells” will also be collected and stored at the hospital. These are the same stem cells
collected from your blood, but stored untreated, in case any problems occur during the procedure. See
paragraph 2 above, “If treatment with Casgevy cannot be completed or fails”.

PHASE 2: The blood stem cells will be sent to the manufacturing site and used to produce Casgevy.
It may take up to 6 months from the time of cell collection to produce and test Casgevy before the medicine
is returned to your doctor.

PHASE 3: Shortly before the stem cell transplant, your doctor will administer a conditioning medicine
in the hospital. This phase will take approximately 2 to 6 days and prepares you for treatment by clearing
cells from the bone marrow so they can be replaced by the modified cells contained in Casgevy. After
receiving this medicine, your blood cell counts will drop to very low levels (see section 4). From this point,
you will remain in the hospital until after the Casgevy infusion.

PHASE 4: One or more vials of Casgevy will be administered to you as an intravenous injection via a
central venous catheter. Central venous catheters are thin, flexible tubes inserted by your doctor into a large vein to access the bloodstream. Risks associated with catheters include infections and blood clot formation. Your doctor and nurses will monitor you closely for any complications related to the central venous catheter.
Administering all injections may take several hours. After receiving Casgevy, you will remain in the hospital so the healthcare team can closely monitor your recovery. This may take approximately 2 months, although the duration may vary. Your doctor will decide when you can return home.

4. Possible side effects

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 may occur within the first days or weeks after treatment, but also much later.

• Pain in the upper right part of the abdomen, under the ribs, yellowing of the eyes or skin, rapid weight gain, swelling of the arms, legs and abdomen, and difficulty breathing. These may be signs of a serious liver disease, called veno-occlusive disease.
• Severe headache, unusual bruising, prolonged bleeding, or bleeding without injury, for example nosebleeds, bleeding from the gums, blood in the urine, faeces or vomit, or coughing up blood. These may be signs of thrombocytopenia, low levels of platelets, which can reduce the blood's ability to clot and may cause bleeding.
• Fever, chills or infections. These may be signs of neutropenia, low levels of white blood cells called neutrophils that fight infections.

Contact your doctor immediately if you experience any of the side effects listed above.
Other side effects that occur with the mobilisation and collection medicine
Very common (may affect more than 1 in 10 people)

• nausea
• vomiting
• headache
• stomach ache
• muscle or bone pain

Common (may affect up to 1 in 10 people)

• lung disease, with symptoms of sudden chest pain, fever, difficulty breathing and signs of fluid accumulation in the lungs seen on chest X-ray, occurring in sickle cell disease (acute chest syndrome)
• painful sickle cell crisis (sickle cell disease with crisis)
• fever
• high levels of white blood cells (leucocytosis)
• diarrhoea
• mouth and throat pain
• numbness in the mouth
• joint pain
• general pain
• feeling of tiredness
• low levels of potassium in the blood (hypokalaemia)
• low levels of magnesium in the blood (hypomagnesaemia)
• high levels of phosphate in the blood (hyperphosphataemia)

Other side effects that occur with the conditioning medicine
Very common (may affect more than 1 in 10 people)

• fever in the presence of low levels of neutrophils (a type of white blood cell) (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 (leucopenia)
• low levels of potassium in the blood (hypokalaemia)
• high levels of phosphate in the blood (hyperphosphataemia)
• low levels of magnesium in the blood (hypomagnesaemia)
• low levels of phosphate in the blood (hypophosphataemia)
• fluid retention
• headache
• fever
• feeling of tiredness
• nosebleeds
• nausea
• vomiting
• stomach ache
• inflammation of the stomach lining
• constipation
• diarrhoea
• mouth and throat pain
• inflammation of mucous membranes, for example, gums (mucositis)
• reduced appetite
• weight loss
• muscle or bone pain
• dry skin
• skin peeling
• changes in skin and nail colour
• tiny spots of blood under the skin
• rash
• hair loss (alopecia)
• increased levels of bilirubin in the blood, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes (hyperbilirubinaemia)
• increased levels of a liver enzyme (alanine aminotransferase) in the blood

Common (may affect up to 1 in 10 people)

• symptoms similar to a lung infection, such as fever, chills, cough and breathing problems, occurring without signs of lung infection (idiopathic pneumonia syndrome)
• inability of the lungs to deliver oxygen to the blood (respiratory failure)
• difficulty breathing
• infection in the blood (sepsis)
• blood infection caused by Klebsiella bacteria (Klebsiella sepsis)
• lung infections (pulmonary infection)
• mouth infection caused by a fungus (oral candidiasis)
• infection of hair follicles (folliculitis)
• increased heart rate (tachycardia)
• increased levels of liver enzymes (aspartate aminotransferase, gamma-glutamyltransferase) in the blood
• low blood pressure (hypotension)
• low levels of oxygen in the blood (hypoxia)
• liver enlargement
• spleen enlargement
• nerve damage in the arms and/or legs causing pain or numbness, burning and tingling (peripheral neuropathy)
• nerve problems causing pain or numbness, burning and tingling sensations (peripheral sensory neuropathy)
• nerve pain
• problems with sense of taste
• blurred vision
• dry eyes
• hot flushes
• cough
• indigestion
• condition in which stomach acid flows back from the stomach into the oesophagus (gastroesophageal reflux disease)
• bleeding gums
• sore throat
• difficulty swallowing
• inflammation of the large intestine, causing pain and diarrhoea (colitis)
• inflammation of the oesophagus (oesophagitis)
• blood in vomit
• rectal bleeding
• inflammation of the stomach and intestine
• mouth ulcers
• general pain
• pain when urinating
• blood in urine
• missed periods
• bleeding between menstrual cycles
• irregular periods
• pain in the vulva and vagina
• early menopause
• weight gain
• bruising
• feeling of itching
• redness of the skin
• cuts or scratches on the skin
• low levels of all types of blood cells (pancytopenia)
• low levels of reticulocytes, a type of immature red blood cells (reticulocytopenia)
• bleeding in an area of the brain involved in balance and coordination (cerebellar haemorrhage)
• abnormal accumulation of fluid surrounding the brain and spinal cord (hydrocephalus)
• low levels of albumin, a blood protein (hypoalbuminaemia)
• low levels of calcium in the blood (hypocalcaemia)
• joint pain
• prolonged blood clotting time
• elevated level of an inflammation marker (C-reactive protein)
• delayed time for transplanted cells to start growing and producing normal blood cells (delayed engraftment)

Other side effects that occur with Casgevy
Common (may affect up to 1 in 10 people)

• immune system disorder (haemophagocytic lymphohistiocytosis) in which certain types of white blood cells (histiocytes and lymphocytes) accumulate in organs, causing excessive inflammation and tissue destruction. Symptoms may include fever not due to infection and not responding to antibiotics, enlargement of the liver and/or spleen, rash, breathing problems, easy bruising, low blood pressure, kidney abnormalities and heart problems
• difficulty breathing, which may require oxygen to help you breathe, sometimes accompanied by chest pain, fever, chills or cough (acute respiratory distress syndrome)
• symptoms similar to a lung infection, such as fever, chills, cough and breathing problems, occurring without signs 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 (leucopenia)
• low levels of calcium in the blood (hypocalcaemia)
• headache
• sensation of numbness, tingling, prickling (paraesthesia)
• nosebleeds
• rash
• tiny spots of blood under the skin
• fever
• chills
• delayed time for transplanted cells to start growing and producing normal blood cells (delayed engraftment)
• events such as chills and increased heart rate at the time of Casgevy administration (infusion-related reactions)

Tell your doctor or nurse if you experience any of these side effects. Contact your doctor or nurse immediately if any of these side effects worsen.
Reporting of side effects
If you get any side effects, including any not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via 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 Casgevy

The following information is intended exclusively for physicians and nurses.
This medicinal product will be administered to you by a qualified physician or nurse, who is responsible
for the correct storage of the medicine before and after use, as well as for its proper disposal.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on each
vial.
Store frozen at a temperature of ≤ -135 °C for up to two years. Keep the vial(s) in the packaging until the time of thawing. Thaw one vial at a time. Do not thaw until immediately before infusion. Do not refreeze after thawing. After thawing, store at room temperature (20 °C - 25 °C) and infuse within 20 minutes.
This medicine contains human blood cells. Unused medicine must be disposed of in accordance with local guidelines for handling materials of human origin.

6. Package contents and other information

What Casgevy contains

• The active substance is exagamglogene autotemcel. Each mL of Casgevy contains 4–13 × 10⁶ cells (haematopoietic stem cells).
• The other components are a solution used to preserve the frozen cells, containing sodium, dimethyl sulfoxide (DMSO), and dextran 40. See section 2 “What you need to know before receiving Casgevy”.

Description of the appearance of Casgevy and package contents
Casgevy is a semi-transparent dispersion for infusion. Casgevy is supplied in vials containing
from 1.5 mL to 20 mL. One or more vials are packaged in a cardboard box. A single package
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 packages.
Your name and date of birth, along with coded information identifying you as the intended recipient, are printed on each package and each vial.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Vertex Pharmaceuticals (Ireland) Limited
Unit 49, Block 5, Northwood Court, Northwood Crescent,
Dublin 9, D09 T665,
Ireland
Tel: +353 (0)1 761 7299

Manufacturer:
Vertex Pharmaceuticals (Europe) Limited
Unit 49, Block 5, Northwood Court, Northwood Crescent,
Dublin 9, D09 T665,
Ireland
Lonza Netherlands B.V.
Urmonderbaan 20 B
6167 RD Geleen
The Netherlands

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien, България, Česká republika, Danmark, Deutschland, Eesti, España, France, Hrvatska, Ireland, Ísland, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, Malta, Nederland, Norge, Österreich, Polska, Portugal, România, Slovenija, Slovenská republika, Suomi/Finland, Sverige
Vertex Pharmaceuticals (Ireland) Limited
Tél/Tel/Teл/Tlf/Sími/Τηλ/Puh: +353 (0)1 761 7299

Ελλάδα
Vertex Φαρμακευτική Μονοπρόσωπη Ανώνυμη Εταιρία
Τηλ: +30 (211) 2120535

Italia
Vertex Pharmaceuticals (Italy) S.r.l.
Tel: +39 0697794000

This medicinal product has been granted a conditional marketing authorisation. This means that additional data on this medicinal product are required.
The European Medicines Agency will review new information on this medicinal product at least annually, and this patient information leaflet will be updated as necessary.

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.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency's website.

For healthcare professionals only

The following information is intended for healthcare professionals only

Precautions to be taken before handling or administration of the
medicinal product
Casgevy is intended for autologous use only. Do not sample, alter, or irradiate the
medicinal product. Irradiation may result in product inactivation.
This medicinal product contains human blood cells. Healthcare professionals handling Casgevy
must take appropriate precautions (wear gloves, protective clothing, and eye protection)
to prevent potential transmission of infectious diseases.

Receipt and storage of Casgevy

• Casgevy is shipped to the treatment center in a cryocontainer.
• Confirm the patient identification details on the label(s) of the medicinal product and on the batch information leaflet (LIS).
• Store in liquid nitrogen vapours at ≤ -135 °C until thawing and administration.

Preparation prior to administration

• Coordinate the timing of thawing and infusion of Casgevy. Confirm the infusion time in advance and adjust the start time of thawing so that Casgevy is available for infusion when the patient is ready, as Casgevy must be administered within 20 minutes of vial thawing. Thaw and administer one vial at a time.
• Before thawing, confirm that the patient’s identity matches the patient information on the Casgevy vial(s). Do not thaw Casgevy vials if the patient-specific label information does not match the patient for whom the medicinal product is intended.
• A dose of Casgevy may be contained in one or more patient-specific cryopreserved vials. Document all vials and confirm that each vial is within its expiry date using the batch information leaflet (LIS) accompanying the medicinal product.
• Prepare the necessary materials for thawing and withdrawal of the medicinal product from the vial(s). Except for the water bath, these materials are single-use. Prepare sufficient materials to administer each vial:
  o water bath
  o alcohol swabs
  o vial adapter (to allow needle-free withdrawal)
  o 18-micron stainless steel filter
  o 30 mL luer-lock syringe
  o Sodium Chloride Injection 9 mg/mL (0.9%) (5 mL to 10 mL required per vial)
  o 10 mL luer-lock syringe for saline wash

Thawing of Casgevy vials

• If the dose consists of multiple vials, thaw and administer one vial at a time. During thawing of one vial, the remaining vials must remain in the cryocontainer at ≤ -135 °C.
• Thaw each vial at 37 °C using a water bath. Ensure the water bath temperature does not exceed 40 °C.
• Thaw each vial by holding it at the neck and gently rotating clockwise and counterclockwise. The process may take between 10 and 15 minutes. Do not leave the vial unattended during thawing.
• Thawing is complete when no ice crystals are visible in the vial.
• Immediately remove the vial from the water bath once thawed.
• The thawed medicinal product should appear as a translucent cell dispersion, free from foreign particles.
• Infuse within 20 minutes of thawing.
• The thawed medicinal product must not be refrozen.

Administration of Casgevy
Casgevy is for autologous use only. The patient’s identity must match the patient identification details on the Casgevy vial(s). Do not infuse Casgevy if the patient-specific label information does not match the patient for whom the medicinal product is intended.
A patient’s dose may consist of multiple vials. All vials must be administered. The entire volume of each provided vial must be infused. If more than one vial is provided, completely administer each vial before proceeding to thaw and infuse the next one.

1. Application of vial adapter and filter

   • Remove the pull-tab from the vial closure cap; clean the septum with an alcohol swab.
   • Remove the cap from the perforator of the adapter.
   • Using both thumbs and index fingers, push the adapter into the vial septum, applying even pressure until a single click is heard.
   • Pull the adapter upward until resistance is felt and it locks into place.
   • Attach the filter to the vial adapter.

2. Withdrawal of Casgevy from the vial

   • Connect an empty 30 mL syringe to the filter.

   • Withdraw the entire volume of medicinal product from the vial.

   • Remove the syringe containing the medicinal product from the filter and set it aside.

   • Aspirate 5 mL–10 mL of Sodium Chloride Injection 9 mg/mL (0.9%) into the empty 10 mL syringe.

   • Connect the syringe containing saline solution to the filter.

   • Inject the saline solution and remove the empty syringe from the filter. Discard the empty syringe.

   • Connect the syringe containing the medicinal product to the filter.

   • Withdraw the vial contents into the syringe containing the medicinal product, then remove the syringe from the filter.

   • The optional medicinal product/patient identification label may be detached from the batch information leaflet (LIS) and affixed to the syringe.

3. Administration of Casgevy via central venous catheter

   • Casgevy must be administered within 20 minutes of thawing.

   • Perform dual patient identity verification at the bedside by two individuals prior to infusion of each vial.

   • Casgevy is administered as an intravenous bolus.

   • The total volume of Casgevy administered within one hour must not exceed 2.6 mL/kg.

   • Do not use an in-line filter for Casgevy infusion.

   • After administration of each Casgevy vial, flush the primary catheter with Sodium Chloride Injection 9 mg/mL (0.9%).

Repeat the above steps for each remaining vial.

Measures to be taken in case of accidental exposure
In case of accidental exposure, follow local guidelines for handling human-derived material. Work surfaces and materials that may have come into contact with Casgevy must be decontaminated with an appropriate disinfectant.

Precautions for disposal of the medicinal product
Unused medicinal product and all materials that have come into contact with Casgevy (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines for handling human-derived material.