ZYNTEGLO™ (Betibeglogene Autotemcel)

ZYNTEGLO™, also called beti-cel (betibeglogene autotemcel), is a one-time gene therapy for beta thalassemia. It was approved by the U.S. Food and Drug Administration (FDA) in 2022 for eligible children and adults with beta thalassemia major (also known as Cooley's anemia) who are dependent on regular transfusions of red blood cells.

Clinical trials have shown that ZYNTEGLO enables many people to make enough hemoglobin on their own to avoid the need for transfusions.

ZYNTEGLO is customized to each patient. It is made from the patient’s own blood-forming stem cells, which are modified genetically to add a functional copy of the beta-globin gene.

The blood stem cells are mixed together with a viral vector — a lentivirus that does not cause infection — in a special facility. This viral vector, given as an IV infusion, delivers the functioning beta-globin gene into the cells.

Once the genetically modified cells take hold (engraft) in the bone marrow, patients can make healthy red blood cells that contain the functional beta-globin protein.

ZYNTEGLO treatment involves multiple steps that can take up to nine months to a year to complete.

Stem cell collection

Before you receive ZYNTEGLO, you will first receive a medication to “mobilize” your blood stem cells, moving them from your bone marrow to your bloodstream. Two to three days later, the stem cells will be collected from your blood using a process called apheresis. All told, this process takes about a week and may need to be repeated until enough stem cells have been collected.

You can then return home while your stem cells are sent to a manufacturing lab to make the ZYNTEGLO product. This takes about 70 to 90 days.

Conditioning chemotherapy and ZYNTEGLO infusion

When the treated cells are ready, you will be admitted to the hospital for four to six weeks. First, you will receive “conditioning” chemotherapy to eliminate the existing blood stem cells in your bone marrow and make room for the new, genetically modified cells to grow. About a week later, you will receive your genetically modified cells as a one-time intervenous (IV) infusion, similar to a blood transfusion. This takes about an hour.

Monitoring and follow-up

After your infusion, you will remain in the hospital for three to six weeks while your treated stem cells engraft in your bone marrow and start making new red blood cells with functioning beta-globin. Our team will watch you for side effects and treat your symptoms. Once you return home, we will continue to follow you with regular check-ups, including blood tests, for 15 years.

Studies indicate that ZYNTEGLO reduces the need for blood transfusions. In two Phase 3 studies, in which a total of 41 people ages 4 to 34 received ZYNTEGLO, 89 percent no longer needed red blood cell transfusions at follow-up an average of two years later and had normal or near-normal hemoglobin levels.

Previously, these patients had required eight or more regular transfusions per year or at least 100 mL/kg/year of red blood cells. After ZYNTEGLO treatment, patients have not required re-starting transfusions during the study follow-up period, up to almost five years for some patients.

The majority of those treated were able to discontinue chelation therapy or phlebotomy to treat iron overload.

ZYNTEGLO appears to be very safe. The most common side effects on the day of the ZYNTELGO infusion have been increased heart rate and abdominal pain. The chemotherapy that is required ahead of time has multiple short- and long-term risks that are important to discuss with your medical team.

Short-term side effects from chemotherapy include, but are not limited to, mouth sores, nausea, hair loss, low white-blood-cell and platelet counts, and increased risk for infections and bleeding. Longer-term risks include, but are not limited to, infertility, rare organ damage or dysfunction, and rare blood cancers. Your care team will be watching for these complications.

Though no cases have yet been seen, there is a small risk of blood cancer with ZYNTEGLO, as there is after any gene therapy or bone marrow transplant that uses chemotherapy. There is also a small risk of blood cancer related to viral vector gene therapies. We will follow you for at least 15 years after treatment to ensure we identify any problems as early as possible and help you stay healthy.

Fertility preservation

The conditioning chemotherapy drug used before ZYNTEGLO treatment may prevent you from being able to become pregnant or father a child. If you choose, our Fertility Preservation Program can provide counseling, sperm banking, egg freezing, and other options for preserving fertility before treatment begins.

Because ZYNTEGLO is a relatively new treatment, it may take extra time and effort to get the insurance approvals. Boston Children’s Financial Services staff will provide support and assistance in securing the Insurance authorization.

Contact the Blood Disorders Center:

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