What is transfusion-dependent beta thalassemia? 

Beta thalassemia is an inherited blood disorder that affects the production of normal hemoglobin, a protein in red blood cells that carries oxygen to tissues throughout the body. It is caused by mutations in a gene called beta-globin. The most severe form of the disease requires lifelong blood transfusions every two to five weeks (thus these patients are “transfusion-dependent”). Patients must be constantly monitored for complications caused by the disease as well as the transfusions, which cause iron to accumulate in the liver, spleen, heart and other organs.

Learn more about beta thalassemia.

How is gene therapy used to treat transfusion-dependent beta thalassemia in children? 

The only FDA-approved gene therapy for beta thalassemia brings back normal red blood cells. It works by putting functional copies of the abnormal gene into a patient’s own blood stem cells. The red blood cells are then able to make normal or near normal levels of hemoglobin. Other types of gene therapy for beta thalassemia that are being studied edit a different gene that restores good red cell function.

Transfusion-dependent beta thalassemia treatment options at CHOP  

CHOP is the first Qualified Treatment Center offering the only FDA-approved treatment, called Zynteglo. More of these FDA-approved treatments could become available in 2023. At CHOP, the gene therapy is provided through a partnership between the Thalassemia Center, the Sickle Cell and Red Cell Disorders Curative Therapy Center (CuRED), and the Cellular Therapy and Transplant Section (CTTS). A key part of CuRED’s role involves counseling patients with beta thalassemia on whether gene therapy is an appropriate treatment option. CTTS and CuRED work to prepare the patient for gene therapy, which is then administered by CTTS.

FDA-approved gene therapy  

In August 2022, the FDA approved beti-cel (brand name Zynteglo®), the first potentially curative gene therapy for people with transfusion-dependent beta thalassemia. The treatment is manufactured by bluebird bio. The FDA approval was based on clinical trial data from multiple study sites, including CHOP. Janet Kwiatkowski, MD, MSCE, Director of the Thalassemia Center, served as CHOP lead investigator for the three clinical trials that led to the FDA approval, and as overall coordinating investigator for one of the studies. Alexis Thompson, MD, MPH, Chief of the Division of Hematology, was a lead investigator of the phase 3 clinical trials and presented before the FDA Advisory Committee ahead of approval. Stephan Grupp, MD, PhD, Section Chief of the Cellular Therapy and Transplant Section, leads the team that administered the therapy in the trials.

In January 2024, the FDA approved exagamglogene autotemcel (exa-cell, brand name Casgevy™) for the treatment of transfusion-dependent beta thalassemia in patients 12 years and older.

Clinical trials for transfusion-dependent beta thalassemia

There are currently active gene therapy clinical trials for transfusion dependent beta thalassemia: 

• Check back for an up-to-date list of trials