What is the Active Ingredient in Casgevy?

October 9, 2025 •

3 min read

In December 2023, the U.S. Food and Drug Administration (FDA) approved the world's first CRISPR-based therapy, Casgevy, marking a historic shift in treating genetic blood disorders. This groundbreaking approach directly modifies a patient's own cells, which is central to understanding what is the active ingredient in Casgevy.

Quick Summary

The active ingredient in Casgevy is exagamglogene autotemcel, a cellular therapy consisting of a patient's own genetically modified blood stem cells. These cells are edited using CRISPR-Cas9 technology to increase fetal hemoglobin production.

Key Points

Generic Name: The active ingredient in Casgevy is exagamglogene autotemcel, a cellular therapy comprising a patient's own genetically modified blood stem cells.
Genetic Editing: The CRISPR-Cas9 system is used to edit a specific gene, BCL11A, which normally represses fetal hemoglobin production after birth.
Reactivated Hemoglobin: By disrupting the BCL11A gene, the modified stem cells produce high levels of fetal hemoglobin (HbF), which is beneficial for oxygen transport in red blood cells.
One-Time Treatment: Casgevy is a single-dose therapy, though the overall treatment process, including cell collection and pre-conditioning, spans several months.
Disease Correction: The therapy addresses the root cause of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), reducing or eliminating the debilitating symptoms of these conditions.
Autologous Cells: The treatment uses the patient's own cells, which eliminates the need for an external donor and significantly reduces the risk of graft-versus-host disease associated with allogeneic transplants.

Casgevy, also known by its generic name exagamglogene autotemcel, represents a profound leap in medical science, moving beyond traditional pharmaceuticals to use gene-editing technology to treat the root cause of certain genetic diseases. Unlike conventional small-molecule drugs, Casgevy's active component is not a chemical compound but a patient's own blood stem cells that have been permanently edited outside the body.

The Active Component: Exagamglogene Autotemcel

The term exagamglogene autotemcel defines the active ingredient in Casgevy. This name indicates a genetic modification ('Exagamglogene') and that the cells are the patient's own blood-forming stem cells ('Autotemcel'). The process involves collecting hematopoietic stem and progenitor cells (HSPCs) via apheresis, then sending them for specialized gene editing.

The Role of CRISPR-Cas9 Technology

CRISPR-Cas9 is the gene-editing tool used to precisely modify the patient's cells. This technology is used to target a specific region of the BCL11A gene. By creating a break in this gene, Casgevy disrupts its normal function, which is to suppress fetal hemoglobin (HbF) production after birth. The edited stem cells then produce high levels of HbF. When infused back into the patient, these cells repopulate the bone marrow and produce healthy red blood cells with increased HbF, providing the therapeutic benefit for sickle cell disease and beta thalassemia.

Mechanism of Action in Treating Blood Disorders

The increase in fetal hemoglobin (HbF) is crucial for treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). For SCD, high HbF levels prevent the sickling of red blood cells by inhibiting abnormal hemoglobin polymerization, thus reducing painful crises. In TDT, reactivating HbF production helps balance hemoglobin levels, increase total hemoglobin, and can eliminate the need for regular blood transfusions.

The Extensive Treatment Process

Receiving Casgevy is a multi-step process that takes several months. It involves collecting the patient's stem cells, gene editing in a lab, and preparing the patient for the modified cells.

The Casgevy Treatment Journey

The treatment journey includes:

Mobilization and Apheresis: Stem cells are moved from bone marrow into the bloodstream and collected.
Ex Vivo Editing: Collected cells are genetically modified using CRISPR-Cas9 to create exagamglogene autotemcel.
Myeloablative Conditioning: Chemotherapy is administered to clear existing bone marrow cells, allowing the new edited cells to engraft.
Infusion and Engraftment: The edited cells are infused, and the patient remains hospitalized while the cells establish themselves.
Long-Term Follow-up: Patients are monitored for safety and effectiveness.

Casgevy vs. Other Treatments

Comparing Casgevy to other therapies highlights its unique gene-editing approach.


Feature	Casgevy (Exagamglogene Autotemcel)	Hydroxyurea	Lyfgenia (Lovotibeglogene Autotemcel)
Mechanism	CRISPR-Cas9 editing of autologous cells to increase fetal hemoglobin (HbF).	Increases HbF production through a non-genetic mechanism.	Lentiviral vector delivery of an engineered hemoglobin variant to autologous cells.
Treatment Type	One-time, ex vivo cellular gene therapy.	Oral medication, requires daily intake.	One-time, ex vivo cellular gene therapy.
Required Process	Stem cell collection, myeloablative conditioning, and reinfusion.	Ongoing, daily medication regimen.	Stem cell collection, myeloablative conditioning, and reinfusion.
Availability	Approved for eligible patients 12+ with SCD or TDT.	Long-established, widely available.	Approved for eligible patients 12+ with SCD.
Donor Requirement	None (uses patient's own cells).	None.	None (uses patient's own cells).
Risk of Malignancy	No boxed warning for blood cancers, but requires long-term monitoring as with other gene therapies.	Rare risk with long-term use.	Has a boxed warning for hematologic malignancy risk.

Conclusion

The active ingredient in Casgevy is exagamglogene autotemcel, a cellular therapy that genetically modifies a patient's own stem cells using CRISPR-Cas9 technology. This innovative treatment works by editing the BCL11A gene to increase fetal hemoglobin production, addressing the root cause of sickle cell disease and beta thalassemia. While a complex, multi-month process, Casgevy offers a potentially curative, one-time treatment for eligible patients. More information is available on the official Casgevy website.

Frequently Asked Questions

The generic name for Casgevy is exagamglogene autotemcel.

The modified cells produce high levels of fetal hemoglobin (HbF), which improves the function of red blood cells. In sickle cell disease, it prevents sickling, and in beta thalassemia, it corrects the hemoglobin imbalance and boosts overall hemoglobin levels.

CRISPR-Cas9 is the gene-editing tool used to make a precise cut in the BCL11A gene within the patient's stem cells. This edit is what ultimately reactivates the production of fetal hemoglobin.

No, Casgevy is an 'autologous' therapy, meaning it uses the patient's own blood-forming stem cells. This reduces the risk of rejection associated with donor-based transplants.

Casgevy is approved for patients 12 years and older with sickle cell disease (SCD) who have frequent vaso-occlusive crises, and for transfusion-dependent beta thalassemia (TDT).

The Casgevy infusion is given one time, but the overall treatment process, including cell collection, manufacturing, and preparatory chemotherapy, can take many months.

The most common side effects are typically associated with the chemotherapy required before infusion. These include low blood cell counts, mouth sores, nausea, musculoskeletal pain, and fever.