FDA Approves Single-Dose Betibeglogene Autotemcel for Patients With Beta-Thalassemia Who Require RBC Transfusions

The FDA has approved betibeglogene autotemcel (beti-cel; Zynteglo) for adult and pediatric patients who require regular blood cell transfusions.¹

The single-dose treatment is the first approved cell-based gene therapy for this indication. Each treatment is customized using the patient’s own bone marrow stem cells. These are genetically modified to produce functional hemoglobin.

Two multicenter clinical trials supported the FDA’s decision. The primary end point for these trials was transfusion independence, which was defined as when a patient can maintain a pre-determined level of hemoglobin without needing a transfusion for at least 12 months. In these trials, among the 41 patients who received beti-cel, the rate of transfusion independence was 89%.

Patients who inherit the blood disorder beta-thalassemia have lower levels of hemoglobin and red blood cells in their system because of mutations in the bet-globin subunit. In return, insufficient levels of oxygen are delivered throughout the body, inducing dizziness, weakness, fatigue, bone abnormalities, and more serious complications. If a patient reaches transfusion-dependent status, they have reached the most severe form of the condition and they will require life-long red blood cell infusions every 2-5 weeks as standard treatment.²

Unfortunately, life-long red blood cell transfusions come with risks, including problems in the heart, liver, and other organs because of excessive iron build-up in the body.

The mechanism of action behind beti-cel is intended to reduce the number of required transfusions for this population. The cell-based gene therapy works by adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells to allow them to make normal to near normal levels of total hemoglobin without regular transfusions.

“Transfusion-dependent beta-thalassemia is associated with an intense treatment burden and significant health risks related to regular red blood transfusions and iron management,” Alexis A. Thompson, MD, MPH, chief of the Division of Hematology, Children's Hospital of Philadelphia, said in a press release. “As a clinician and an investigator in the [beti-cel] clinical development program, I celebrate the therapeutic potential of this treatment for patients and its implications for the field of gene therapy, all made possible through the incredible courage of patients and families who participated in the clinical trials.”

Because the therapy is complex in nature, beti-cel will only be available at qualified treatment centers. These institutions will be selected based on their known expertise in areas including stem cell transplantation, cell and gene therapy, and beta-thalassemia. These centers will be given specialized training prior to being authorized to administer betibeglogene autotemcel. During administration, patients will need to be monitored for hypersensitivity reactions, thrombocytopenia, and bleeding.

The most common adverse events associated with treatment include reduced platelet and other blood cell levels, as well as mucositis, febrile neutropenia, vomiting, pyrexia (fever), alopecia (hair loss), epistaxis (nosebleed), abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder and pruritus (itch).

Investigators noted that there is a risk of blood cancer associated with this treatment strategy, however, this has not been observed with beti-cel. After undergoing treatment, patients should have their blood monitored for at least 15 years to assess for any evidence of cancer.

References

1. FDA approves first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular blood transfusions. News release. FDA. August 17, 2022. Accessed August 18, 2022. https://bit.ly/3C9Mpjh
2. bluebird bio announces FDA approval of Zynteglo the first gene therapy for people with beta-thalassemia who require regular red blood cell transfusions. News release. bluebird bio, Inc. August 17, 2022. Accessed August 18, 2022. https://bit.ly/3JZHSSx