Casgevy

Pronunciation: cass-JEH-vee
Generic name: exagamglogene autotemcel
Dosage form: suspension for intravenous infusion
Drug class: Miscellaneous uncategorized agents

Medically reviewed by Carmen Pope, BPharm. Last updated on Jan 17, 2024.

Casgevy (exagamglogene autotemcel) is a gene therapy that is given as a one-time intravenous infusion to treat adults and children aged 12 years and older with:

• Sickle cell disease with recurrent vaso-occlusive crises (VOCs).
• Transfusion-dependent β-thalassemia (TDT).

VOCs are when sickled red blood cells block blood flow, depriving tissues of oxygen. Sickle cell disease (SCD) is a common genetic disease that results from a mutation in the gene, BCL11A , encoding the beta chain of adult hemoglobin (HbA). Fetal hemoglobin (HbF) is the type of hemoglobin that carries oxygen while we are growing in the womb. Shortly after we are born, we start replacing HbF with HbA. People with SCD make defective HbA that turns into sickle shapes and symptoms start when the person's body starts to make less HbF and more HbA.

TDT is the most severe form of beta-thalassemia and patients require lifelong regular red blood cell transfusions to survive. If left untreated, the disease can damage organs and potentially lead to death. It is caused by mutations in the β-globin (HBB) gene that result in significantly reduced or absent production of functional adult beta (β)-globin, a component of hemoglobin.

Casgevy uses a person’s own blood stem and progenitor cells which are collected and sent for editing using non-viral, CRISPR/Cas9 technology, so no donor is needed. The technology finds and edits the parts of the DNA containing the BCL11A gene to reduce its activity. The edited cells are then infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT) after myeloablative busulfan conditioning. This means the patient continues to make more HbF and less HbA which has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

Casgevy was FDA approved on December 8, 2023.

Warnings

Casgevy may cause hypersensitivity reactions during or after the infusion. Your doctor will monitor you for these.

There is a risk of neutrophil engraftment failure after HSC transplant and Casgevy administration which may require rescue treatment with your collection of unmodified CD34+ cells. In clinical trials all treated patients achieved neutrophil engraftment and none needed rescue CD34+ cells.

Longer median platelet engraftment times were observed with Casgevy treatment compared to an allogeneic HSC transplant. Until then there is an increased risk of bleeding. Your doctor will monitor you for bleeding and check your platelet counts. In clinical trials, there was no association observed between serious bleeding and time to platelet engraftment.

There is a risk of off-target gene editing in CD34+ cells due to uncommon genetic variants although this has not yet been reported.

Before taking

After receiving the conditioning 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.

How is Casgevy administered?

Casgevy is made specifically for each patient.

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment. Talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

There are 4 main steps involved with Casgevy treatment.

Step 1: Before treatment, a doctor will give you a mobilization medicine. This medicine moves blood stem cells from your bone marrow into the bloodstream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step ‘rescue cells’ are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If Casgevy cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from Casgevy.

Step 2: After they are collected, 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 before it is sent back to your healthcare provider.

Step 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in the hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in Casgevy. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the Casgevy infusion.

Step 4: One or more vials of Casgevy will be given into a vein (intravenous infusion) over a short period. After the 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.

Related/similar drugs

Reblozyl, Zynteglo, Oxbryta, luspatercept, voxelotor, Lyfgenia, lovotibeglogene autotemcel

What should I avoid after receiving Casgevy?

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

What are the side effects of Casgevy?

After treatment with Casgevy, you will have fewer blood cells for a while, until the treatment 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 doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

You may also experience side effects associated with other medicines administered as part of the Casgevy treatment regimen. Talk to your physician regarding those possible side effects

The most common side effects include:

• Mucositis (inflammation of the inside of the mouth and gums)
• Febrile neutropenia (fever ≥ 101.3°F (38.5°C) and an absolute neutrophil count (ANC) < 500 cells/mm³ or an expected decrease of ANC to < 500 cells per mm³ in the next 48 h)
• Decreased appetite
• Low levels of platelet cells, which 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 doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What other drugs will affect Casgevy?

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.

Manufacturer

Vertex Pharmaceuticals Incorporated.

Casgevy Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Casgevy.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer