What Is It, and Why Does It Matter?
Casgevy (exagamglogene autotemcel) is a one-time gene therapy that uses a patient's own blood-forming stem cells. It helps people with certain medical conditions to make healthy red blood cells on their own. These conditions include sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT). The FDA has now approved Casgevy for children as young as 2 years old. Before, it was only approved for people 12 years and older.
SCD is a blood disease you are born with. It makes red blood cells hard and shaped like a sickle (a curved farm tool), instead of round and soft. These sickle-shaped cells can block blood vessels and lower the amount of oxygen that reaches the body. This can cause sudden attacks of severe pain, called vaso-occlusive crises. These cells can also damage important organs, like the brain, heart, lungs, and kidneys. This can shorten a person's life and often means frequent hospital visits and lifelong medical care.
If you have TDT, your body can't make enough healthy hemoglobin, which is the protein in red blood cells that carries oxygen. People who have this blood disease need regular blood transfusions, often starting when they are very young. These transfusions save lives, but they can cause iron to build up in the body. Too much iron can harm the heart, liver, and other organs. People with TDT also need ongoing treatment to remove extra iron and manage their symptoms.
Casgevy uses your body's own blood-forming stem cells to treat these conditions. These are called hematopoietic stem cells (HSCs). Your health care team collects these cells from you. A lab then uses a tool called CRISPR/Cas9 to edit the cells. Before you get the edited healthy cells back, you will have treatments that clear out the cells in your bone marrow. Then the edited cells are given to you through a vein (IV). The edited cells increase your levels of a type of hemoglobin called fetal hemoglobin (HbF). Higher HbF levels can help red blood cells keep their normal round shape. This may help prevent severe pain crises in SCD. It may also raise total hemoglobin levels and reduce or end the need for frequent transfusions in TDT.
Why Was It Approved?
The FDA's decision to approve Casgevy in younger children was based on two very small studies in children ages 5-11. In order to know whether the treatment is working, each child must be monitored for at least 16 months after receiving Casgevy. But not all of the children in these studies received Casgevy more than 16 months ago. Some of them are still being monitored to see how well the treatment worked.
The first study included 15 children with TDT. Of those who had been monitored long enough to evaluate the effects of Casgevy, most went at least 12 months without needing a transfusion. The second study included 11 children with SCD. Of those who were monitored long enough to evaluate the effects of treatment, all went at least 12 months without a severe pain crisis.
In both studies, the most common serious side effects were mouth and throat soreness (mucositis) and fever with a low white blood cell count (febrile neutropenia). Loss of appetite was also common in people with SCD.
Since these conditions can be very serious and these results are promising, the FDA granted approval of Casgevy to children as young as 2 years old. All children in these studies will continue to be monitored. They were also asked to join a long-term study for up to 15 years. This will help track how well the treatment lasts and watch for safety issues over time.
What Do I Need to Know?
Casgevy is given one time, through a vein (IV). First, your care team collects your stem cells (HSCs) and sends them out to be edited. Before you get the edited cells back, you receive strong chemotherapy called myeloablative conditioning. This clears space in your bone marrow for the edited cells. Preparing the edited cells can take up to six months. After your infusion, you may stay in the hospital for about four to six weeks so your care team can watch you closely.
Clearing out your bone marrow can increase your risk of serious health problems. When your platelet count is low, your risk of bleeding is high. Call your health care provider right away if you have a severe headache, unusual bruising, or bleeding that will not stop. When your white blood count is low, your risk of infection is high. Tell your health care provider right away about fever, chills, or other signs of infection.
Some people may have an allergic reaction, including a serious reaction called anaphylaxis. There is also a risk that your white blood cells will not grow back as expected. This is called neutrophil engraftment failure. Your care team will track your blood counts and treat any infections. If needed, they can give you backup stem cells (CD34+ cells).
Some medicines, like hydroxyurea and crizanlizumab, need to be stopped for at least eight weeks before cell collection and conditioning. Medicines that remove extra iron (called iron chelators) must be stopped at least seven days before conditioning. In some cases, blood removal (phlebotomy) can be used instead of chelators. Speak with your health care provider about all medicines, supplements, and over-the-counter drugs you are taking.
You will need to plan ahead for pregnancy and fertility. You cannot receive Casgevy while pregnant because of the risks from the medications used for conditioning. You will need a negative pregnancy test before each cell collection cycle and again before conditioning. Use effective birth control starting when cell collection begins, and for at least six months after your infusion. Conditioning may affect your ability to have children later. Talk with your health care provider about ways to protect your fertility before treatment.