Casgevy

Casgevy (exagamglogene autotemcel) is a one-time autologous genome-edited hematopoietic stem cell-based gene therapy used to treat patients 2 years and older with:

• Sickle cell disease (SCD) who have frequent vaso-occlusive crises (VOCs).
• βeta-thalassemia (β-thal) who need regular blood transfusions.

Casgevy is made specifically for each patient, using the patient's own blood stem cells, so a donor is not needed. In the lab, CRISPR/Cas9 gene editing switches off part of the BCL11A gene. This reactivates fetal hemoglobin (HbF), the oxygen-carrying hemoglobin made before birth. Higher HbF raises overall hemoglobin levels and improves the production and function of red blood cells. After busulfan conditioning, the edited cells are infused back into the patient. Increased HbF can eliminate painful vaso-occlusive crises in people with sickle cell disease and remove the need for regular blood transfusions in people with beta-thalassemia.

Casgevy first received FDA approval on December 8, 2023, for patients 12 years and older. Approval was extended on July 01, 2026, to include children 2 years and older. Patients with SCD should weigh at least 12 kg before mobilization begins, since those below this weight may struggle to reach the minimum target cell dose.

After treatment with Casgevy, you will have fewer blood cells for a while, until Casgevy takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your healthcare provider will monitor this and give you treatment as required. The healthcare provider will tell you when blood cell levels return to safe levels.

• Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelet cells: severe headache abnormal bruising prolonged bleeding bleeding without injury, such as nosebleeds, bleeding from gums, blood in your urine, stool, or vomit, or coughing up blood.
• Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of white blood cells: fever chills infections.

You may experience side effects associated with other medicines administered as part of the Casgevy treatmentregimen. Talk to your healthcare provider regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

The most common side effects of Casgevy are:

• Low levels of platelets may reduce the ability of blood to clot and may cause bleeding
• Low levels of white blood cells, which may make you more susceptible to infection.

Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

• fever
• chills
• infections
• severe headache
• abnormal bruising
• prolonged bleeding
• bleeding without injury, such as nosebleeds, bleeding from gums, blood in your urine, stool, or vomit, or coughing up blood.

These are not all the possible side effects of Casgevy. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Your healthcare provider will give you other medicines, including a chemotherapy medicine, as part of your treatment with Casgevy. It's important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the chemotherapy medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

Casgevy is made specifically for you from your own blood stem cells. Receiving Casgevy is a multi-step process:

• Your healthcare provider will collect your blood stem cells through a process called mobilization and apheresis. This process may happen more than once. Each time, it can take up to one week. Back-up cells are also collected and stored at the hospital. These are kept and may be given to you in case there is a problem in the treatment process. If you receive backup cells, you will not have any benefit from Casgevy.
• Your collected blood stem cells will be sent to the manufacturing site, where they are used to make Casgevy. Manufacturing may take up to 6 months.
• Shortly before you receive Casgevy, you will be admitted to the hospital. Your healthcare provider will give you chemotherapy medicine for a few days to make room in the bone marrow for your edited stem cells. After you are given this medicine, your blood cell levels will fall to very low levels.
• One or more vials of Casgevy will be given into a vein (intravenous infusion).
• After the Casgevy infusion, you will stay in the hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

• Do not donate blood, organs, tissues, or cells at any time in the future.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, antacids, and herbal supplements.

Your doctor will advise you to avoid the following medications:

• Disease-modifying therapies used for SCD, such as hydroxyurea, crizanlizumab, and voxelotor. Discontinue 8 weeks before the planned start of mobilization and conditioning
• Iron chelation therapy. Stop at least 7 days before myeloablative conditioning. If iron chelation is required, the use of non-myelosuppressive iron chelators should be avoided for at least 3 months after Casgevy administration, and the use of myelosuppressive iron chelators should be avoided for at least 6 months after administration. Phlebotomy can be used instead when appropriate.
• Granulocyte-colony stimulating Factor (G-CSF) must not be used for CD34+ HSC mobilization of patients with SCD.

No formal drug interaction studies have been performed, but Casgevy is not expected to interact with the hepatic cytochrome P-450 enzymes or drug transporters.

This is not a full list of interactions. See the prescribing information for a full list.

Casgevy (exagamglogene autotemcel) is manufactured for Vertex Pharmaceuticals Incorporated; 50 Northern Avenue, Boston, MA 02210.