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What if treating sickle cell disease (SCD) didn’t have to mean ongoing appointments, infusions, or hospital stays? For some people with SCD, a one-time treatment may offer the possibility of long-term relief from certain complications. But it’s a big decision. What does the treatment involve, and what should you know about the risks, benefits, and challenges?
Two gene therapies, exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia), are approved by the U.S. Food and Drug Administration (FDA) to treat SCD. The treatments have different eligibility requirements, but both use the person’s own blood-forming stem cells.
However, Casgevy and Lyfgenia use different approaches to treat SCD. Choosing between these treatments depends on guidance from your healthcare team. This article will go over how each therapy works, what they have in common, and how they differ.
SCD is a genetic blood disorder that affects your hemoglobin, the protein in red blood cells that carries oxygen. People with SCD make abnormal hemoglobin S, which can cause red blood cells to become stiff and sickle-shaped (curved like a crescent moon) after they release oxygen.
Sickle-shaped cells can make it harder for your blood to flow throughout your body, which can cause painful episodes called vaso-occlusive crises. Casgevy and Lyfgenia address this problem in different ways. Casgevy increases fetal hemoglobin, a type of hemoglobin your body makes before birth, while Lyfgenia helps your body make a modified form of hemoglobin that reduces sickling.
Fetal hemoglobin helps keep red blood cells from becoming sickle-shaped. Higher levels of fetal hemoglobin can help reduce sickling and improve how red blood cells carry oxygen. Studies have found that people with higher levels of fetal hemoglobin may have fewer pain crises, milder disease, and a lower risk of problems such as leg ulcers and acute chest syndrome. They may also live longer.
Casgevy uses gene editing to help the body make more fetal hemoglobin. This helps prevent red blood cells from sickling because fetal hemoglobin interferes with the process that causes sickling. The treatment focuses on a gene called BCL11A, which, when its function is reduced, can increase fetal hemoglobin in the body.
Casgevy uses the person’s own blood-forming stem cells. The treatment process begins with collecting your blood-forming stem cells through a process called apheresis. The cells are then edited in a lab before being infused back into your body.
Lyfgenia uses a viral vector, or modified virus, to deliver a gene into a person’s blood-forming stem cells. The new gene allows the modified stem cells to produce red blood cells containing an adult hemoglobin called HbA T87Q, which helps prevent sickling.
Casgevy edits genetic instructions that are already in the stem cells, while Lyfgenia adds new genetic instructions. Both use genetic changes to help the body make hemoglobin that is less likely to allow red blood cells to sickle.
Both Casgevy and Lyfgenia are cell-based gene therapies that share a similar treatment journey. Neither treatment is a simple infusion that takes place at a doctor’s office or infusion center. Both require a step-by-step process similar to a traditional stem cell transplant.
While your healthcare team completes tests to see whether gene therapy is right for you, you may begin receiving regular blood transfusions. These may be simple transfusions or exchange transfusions, which replace some of your sickled red blood cells with healthy ones. You may receive transfusions for several months before stem cell collection and while waiting for your gene therapy infusion.
First, doctors collect blood-forming stem cells from your blood. This is done through a process called apheresis and may require an overnight stay. The blood is passed through a machine that separates out the stem cells. The rest of the blood is then returned to you.
Your doctor will have you stop taking hydroxyurea before stem cell collection and may also ask you to stop taking certain other medications. This allows your body to make plenty of stem cells for collection. The collected stem cells are then sent to a laboratory. It is important to collect enough stem cells. If the first collection doesn’t provide enough cells, another apheresis procedure may be necessary.
In the laboratory, the treatment process takes different paths depending on which treatment you’ll be receiving. For Casgevy, this is the step where the stem cells are edited to increase the production of fetal hemoglobin.
For Lyfgenia, a modified virus delivers a gene to the stem cells that allows them to make a form of hemoglobin that helps prevent red blood cells from becoming sickle-shaped.
The gene editing or adding process can take several months in the lab. After this is completed, the modified cells are then prepared to be infused back into your body.
To prepare the cells to be infused back into your body, you’ll receive myeloablative conditioning. This process involves high-dose chemotherapy to remove existing blood-forming stem cells from your bone marrow, making room for the modified stem cells.
Myeloablative conditioning is an important part of both therapies. It also has risks and side effects. That’s why you’ll stay in the hospital, where your healthcare team can closely monitor you for side effects and treat them quickly. You may experience low blood counts, infections, and other complications, including pain. You will usually stay in the hospital for several weeks so your healthcare team can monitor you.
After myeloablative conditioning, the modified stem cells are given back to you through a one-time intravenous infusion in the hospital. The cells travel to the bone marrow and begin engraftment. This means the cells settle into the bone marrow to start making new blood cells.
You’ll be closely monitored during this period of treatment. You may need supportive care or blood transfusions while your blood counts recover. You and your caregivers will need to plan for time away from work, school, and normal activities. You can expect to stay in the hospital for several weeks until your blood counts recover enough for you to go home.
Gene therapy is different from a traditional bone marrow transplant, which uses stem cells from a donor. Because gene therapy uses your own cells, it eliminates the risk of graft-versus-host disease, a complication that occurs when donated immune cells attack your body’s healthy tissues.
Your treatment doesn’t end when you leave the hospital after your infusion. Both therapies require long-term follow-up with your doctor or hematologist. Your healthcare team will continue to monitor your blood counts, hemoglobin levels, and SCD symptoms.
Casgevy and Lyfgenia were tested in separate clinical studies with different eligibility requirements, follow-up periods, and outcomes. For that reason, it’s hard to say that one treatment is more effective than the other.
Casgevy is approved for people with SCD and recurrent vaso-occlusive crises. In July 2026, the FDA expanded its approval to include children as young as 2 years old.
Lyfgenia is approved for people aged 12 years and older with SCD who have a history of vaso-occlusive events.
Both therapies have risks related to the high-dose chemotherapy used before the stem cell infusion. However, Lyfgenia has an additional safety warning.
The FDA requires a boxed warning for Lyfgenia because some people who received the treatment have developed blood cancers or other serious blood disorders, including acute myeloid leukemia and myelodysplastic syndrome. People who receive Lyfgenia need lifelong monitoring for signs of blood cancer.
Casgevy doesn’t carry the same boxed warning. However, it also requires high-dose chemotherapy and close, long-term safety monitoring. Because Casgevy edits your DNA, the FDA warns about the possibility of unintended, or off-target, gene editing.
Fertility is an important topic to talk to your doctor about before starting either treatment. The high-dose chemotherapy used to prepare your body to receive the modified stem cells can damage reproductive cells. This may cause infertility, or the inability to have children.
This risk may bring up the possibility of fertility preservation before treatment starts. Depending on your age and overall health, you may be able to explore fertility preservation options, such as sperm banking and egg or embryo freezing.
Talk to your healthcare team before the treatment process starts if you’d like to have biological children in the future. They may be able to help guide you on fertility preservation or discuss other treatment options that may be a better fit for you and your family.
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