The U.S. Food and Drug Administration (FDA) approved Casgevy^™ (exagamglogene autotemcel) suspension for intravenous (IV) infusion on Dec. 8, 2023. It is the first approved drug that uses clustered regularly interspaced short palindromic repeats (CRISPR) to repair defective genes. Also known as exa-cel during development, Casgevy is indicated to treat sickle cell disease (SCD) for patients who are at least 12 years old and experience repeated episodes of vaso-occlusive crises (VOCs), which also are called vaso-occlusive events (VOEs) or sickle cell crises. Stem cells removed from each patient are altered to include functioning genes that produce normal red blood cells (RBCs). Processing of the cells may take up to six months. Patients undergo chemotherapy (chemo) to eliminate the defective blood cell genes and then Casgevy is administered as one intravenous (IV) infusion that contains at least 3 × 106 CD34+ cells/kg. It must be given by trained healthcare providers in only a few specially equipped medical centers around the United States, and patients must stay in the hospital for several weeks after the infusion to allow immune function to recover. The cost is $2.2 million, but a launch date has yet to be revealed. For its prescribing information, look here.

At a Glance

• Brand (Generic) Name: Casgevy(exagamglogene autotemcel, exa-cel)
• Manufacturer: Vertex Pharmaceuticals/CRISPR Therapeutics
• Date Approved: Dec. 8, 2023
• Indication: for the treatment of SCD in patients 12 years and older who have repeated VOCs
• Dosage Forms Available: cell suspension that includes at least3 × 10⁶ CD34+ cells/kg for IV infusion
• Launch Date: Not available

• Estimated Cost: $2.2 million
• According to the Centers for Disease Control and Prevention (CDC), SCD is the most common hereditary condition in the United States, affecting up to 100,000 Americans. Vertex and CRISPR estimate that around 16,000 U.S. patients may be candidates for treatment with Casgevy.
• Most U.S. patients who have SCD are of African ancestry, but individuals of southwest Asian, Middle Eastern, Hispanic, or southern European heritage also may have the condition.
• SCD is a genetic disorder that causes normally pliable, round RBCs to deform into a characteristic crescent or sickle shape and makes them less flexible. Sickled cells do not survive as long as regular RBCs, so patients who have SCD have anemia, too. Other complications can include bone pain, delayed growth, infections, kidney disease, low body weight, sores on the legs, and swollen hands and feet.
• The most common complication of SCD is VOCs, which are caused when small blood vessels are blocked by sickled RBCs in any part of the body. Eventually, internal organs sustain significant damage. Dehydration, extreme heat or cold, illness, and stress can bring about VOCs, which also may happen spontaneously and unpredictably. The intense pain associated with them is the main reason that patients who have SCD are hospitalized and/or need emergency room services.
• Casgevy alters the patient’s stem cells to promote the production of fetal hemoglobin, which results in functional, normally shaped RBCs.
• In the year before being treated with Casgevy, the 30 patients who were included in a clinical trial averaged four periods of severe pain and three hospital stays. After the procedure, 29 remained free of severe SCD-related pain for at least one year.
• Because patients receiving Casgevy usually have low counts of platelets and white blood cells, they may bleed and bruise easily and be more likely to have infections.
• Since screening for SCD is mandatory at birth, treatment for it usually begins very early in life.
• Most current drug treatments for SCD only manage its symptoms and complications; they do not affect the underlying causes of the condition. They include antibiotics, blood transfusions, and pain medications. Oral l-glutamate and hydroxyurea products help to prevent VOCs.
• The first drug to treat the cause of SCD, Oxbryta^™ (voxelotor – Global Blood Therapeutics) tablets was FDA approved in late 2019. The first sickle hemoglobin polymerization inhibitor, Oxbryta sticks to hemoglobin, attracting more oxygen and stabilizing RBCs. Additionally, it may decrease the thickness of blood and the tendency of blood cells to sickle while also increasing RBC flexibility. It is taken orally once a day.
• Also in 2019, Adakveo^® (crizanlizumab-tmca – Novartis) was FDA-approved to treat VOCs for patients 16 years of age and older who have SCD. A first-in-class P-selectin inhibitor, Adakveo blocks the activity of a cell adhesion protein involved in VOC, keeping blood cells from clumping and helping to maintain blood flow. It is administered by a healthcare professional as a 30-minute intravenous (IV) infusion once every four weeks after two loading doses.
• Also on Dec. 8, 2023, the FDA approved Lyfgenia (lovotibeglogene autotemcel – bluebird bio), another gene therapy that treats SCD with VOCs. It uses a non-infective virus to introduce effective β-globin genes that make normal RBCs.
• Casgevy was approved under the FDA’s Fast Track and Priority Review initiatives. It also qualified as both a Regenerative Medicine Advanced Therapy (RMAT) and an Orphan Drug.
• Casgevy is also under FDA review as a treatment for patients 12 years and older with transfusion-dependent beta-thalassemia. FDA is expected to complete its review for this use by Mar. 30, 2024.