Casgevy: First CRISPR Gene Therapy Approved for Sickle Cell Disease

How Does Casgevy Work as a Gene Therapy?

Casgevy (exagamglogene autotemcel) works by harvesting a patient's hematopoietic stem cells and using CRISPR-Cas9 gene-editing technology to make a precise cut in the BCL11A gene. This gene normally suppresses fetal hemoglobin (HbF) production after birth. By disrupting BCL11A, the edited stem cells produce high levels of HbF when reinfused into the patient, compensating for the defective or absent adult hemoglobin that causes sickle cell disease or beta-thalassemia.

Before receiving the modified cells, patients undergo myeloablative conditioning with busulfan chemotherapy to clear existing bone marrow. The edited stem cells are then infused intravenously and engraft in the bone marrow, where they begin producing red blood cells with elevated fetal hemoglobin. This process requires hospitalization for approximately 4 to 6 weeks and close monitoring for engraftment and potential complications such as infection during the period of low blood counts.

In the pivotal CLIMB SCD-121 trial, 29 of 30 evaluable sickle cell patients were free from severe vaso-occlusive crises for at least 12 consecutive months following treatment. For beta-thalassemia patients in the CLIMB THAL-111 trial, 39 of 42 patients achieved transfusion independence. These results represent a potential functional cure for diseases that collectively affect millions of people worldwide, with approximately 100,000 Americans living with sickle cell disease alone.

Who Is Eligible for Casgevy Treatment?

The FDA approved Casgevy in December 2023 for patients aged 12 and older with sickle cell disease characterized by recurrent vaso-occlusive crises. The EMA granted conditional marketing authorization for the same indication and also for transfusion-dependent beta-thalassemia in patients 12 years and older. Patients must be medically fit to undergo myeloablative conditioning with busulfan, which is an intensive chemotherapy regimen required before stem cell reinfusion.

Candidates for Casgevy undergo a thorough evaluation including cardiac, pulmonary, hepatic, and renal function assessments. Patients with significant organ damage from their underlying disease may still qualify but require careful risk-benefit analysis. The treatment is administered at authorized treatment centers with expertise in stem cell transplantation and gene therapy, and as of 2025, only a limited number of centers in the United States and Europe are qualified to deliver this complex therapy.

Sickle cell disease disproportionately affects people of African, Mediterranean, Middle Eastern, and South Asian descent. In the United States, it is most prevalent among Black Americans, occurring in approximately 1 in 365 Black births. The global burden is substantial, with an estimated 300,000 children born with sickle cell disease annually worldwide, predominantly in sub-Saharan Africa where access to advanced therapies remains severely limited.

What Are the Costs and Access Challenges?

Vertex Pharmaceuticals set the list price of Casgevy at $2.2 million for a single treatment course, positioning it among the most expensive therapies in history. The company argues this represents value given the lifelong costs of managing sickle cell disease, estimated at $1.6 million to $1.7 million per patient over a lifetime including hospitalizations, blood transfusions, pain management, and treatment of organ damage. Several health economics analyses, including those by the Institute for Clinical and Economic Review (ICER), have assessed the cost-effectiveness at various price points.

Insurance coverage remains a significant hurdle. While CMS has indicated willingness to cover gene therapies for Medicare and Medicaid beneficiaries, many patients face complex prior authorization processes and potential out-of-pocket costs. Vertex has established a patient assistance program and is negotiating outcomes-based agreements with payers, where reimbursement is tied to treatment success. Some states are exploring innovative financing models such as installment payments spread over multiple years.

The global access challenge is even more stark. The vast majority of sickle cell disease patients live in low- and middle-income countries, particularly in sub-Saharan Africa, where healthcare infrastructure cannot support the complex manufacturing and administration requirements of Casgevy. The treatment requires apheresis for stem cell collection, advanced laboratory facilities for gene editing, and specialized transplant units for patient care. International organizations including the WHO are calling for strategies to make gene therapies accessible beyond wealthy nations.