LYFGENIA™ Gene Therapy for Sickle Cell Disease

LYFGENIA is a one-time gene therapy treatment for people age 12 years or older with sickle cell disease and a history of vaso-occlusive pain crises. It has been found to decrease or eliminate vaso-occlusive pain crises in many people.

LYFGENIA is custom-made for each person using their own blood-forming stem cells. A delivery vehicle (vector), consisting of a harmless virus, is used to add working copies of the beta-globin gene to the stem cells. Once treated, the cells are returned to the body, where they begin making red blood cells with healthy non-sickle hemoglobin. These new red blood cells are less likely to sickle and clog blood vessels.

Yes. The U.S. Food and Drug Administration approved LYFGENIA in December 2023 for patients with sickle cell disease age 12 years and older.

LYFGENIA is a custom treatment, made from each person’s own blood stem cells. It involves multiple steps that may take up to nine months to a year to complete.

Blood transfusions

Beginning three months before stem cell collection, you will start or continue to receive regular red blood cell transfusions.

Stem cell collection

Before you receive LYFGENIA, you will be admitted to the hospital for collection of stem cells from your blood, a process that can take up to four to five days.

First, a special catheter will be placed in one of your veins under sedation. You will receive a medication to “mobilize” your blood stem cells, moving them from your bone marrow to your bloodstream. The stem cells will then be collected from your blood using a process called apheresis. Then the catheter will be removed.

You can then return home while your stem cells are edited in a special manufacturing lab to make the custom LYFGENIA product. This will take several months. Sometimes additional cycles of stem cell collection will be needed to collect enough cells for the gene therapy.

Conditioning treatment and LYGENIA infusion

When the treated stem cells are ready, you will have several days of testing to make sure you are ready for the treatment. You will be admitted to the hospital for four to six weeks. Before receiving LYFGENIA, you will receive high-dose “conditioning” chemotherapy. The powerful conditioning drug eliminates the stem cells with the sickling trait in your bone marrow and makes room for the new, treated cells. About a week later, you will receive your treated cells as a one-time infusion. 

Monitoring and follow-up

After your infusion, you will remain in the hospital while your treated stem cells take hold (engraft) in your bone marrow and start making new blood cells — including red blood cells with healthy, non-sickling hemoglobin. Our team will watch you for any side effects. Once you return home, we will continue to follow you with regular check-ups for 15 years.

Note: While LYGENIA is generally safe, a few patients have developed blood cancers. Your care team can help you weigh this risk. Because blood cancers may take many years to develop, we monitor people receiving LYFGENIA with blood tests every six months for 15 years afterward. Symptoms to watch for include:

• Abnormal bruising or bleeding (including nosebleeds)
• Blood in urine, stool, or vomit, or coughing up blood
• Severe headache
• Unusual stomach or back pain
• Fever
• Swollen glands
• Tiredness

Because of the conditioning chemotherapy needed before you receive LYFGENIA, you will temporarily have low levels of platelets (the cells that make your blood clot), red blood cells, and white blood cells (which fight infection). Levels should go back to normal once the treated stem cells have a chance to engraft into your bone marrow and begin making new blood cells. You will also lose your hair temporarily.

After your LYFGENIA infusion, you will stay in the hospital until your blood counts build back up. Our care team will be watching for these side effects:

• Abnormal bruising, bad headaches, prolonged bleeding, or bleeding from the gums or in urine or stool (signs of a low platelet count)
• Fever, chills, or infections (signs of a low white-cell count)

Other side effects of the conditioning chemotherapy may include severe, painful sores of the lips, mouth, and throat; nausea; muscle or bone pain; abdominal pain; vomiting; headache; and itching. These symptoms are temporary and our care team can treat these as needed.

As in cancer treatment, the strong conditioning chemotherapy used before LYFGENIA treatment may prevent you from being able to become pregnant or father a child. Your care team will offer referral to our Fertility Preservation Program before you start treatment. This program provides counseling, sperm banking, egg freezing, and other options for preserving fertility.

LYFGENIA was tested in a two-year multicenter clinical trial in patients aged 12 to 50 years who had sickle cell disease and history of vaso-occlusive events. Twenty-eight of 32 patients were evaluated six to 18 months after their LYFGENIA treatment were completely free of vaso-occlusive events. Three years after treatment, the majority of patients described meaningful improvements in pain intensity, pain interference with activities and sleep, and fatigue.

The study also treated five adults with sickle cell disease and a history of stroke or vasculopathy. Before receiving LYFGENIA, all needed frequent transfusions. At 44 to 60 months’ follow-up, all five were transfusion-independent and had not had further strokes.

The LYFGENIA clinical trial is still ongoing. So far, the data indicate that in people with sickle cell disease, LYFGENIA can eliminate or greatly reduce the severity of pain crises, making it a milder disease in most people.

Because LYFGENIA has only recently become available, it’s not yet clear to what extent insurance providers will cover it. We encourage you to talk with your health insurance company and medical team. Boston Children’s Financial Services staff will guide you through the insurance approval process. 

Contact the Blood Disorders Center:

Phone: 617-355-8246
Email: hemeclinic-dl@childrens.harvard.edu