FDA Approves Zynteglo for Patients with Beta-thalassemia Requiring Regular Blood Transfusions

The FDA approved betibeglogene autotemcel (Zynteglo; bluebird bio) for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions, making it the first cell-based gene therapy for treatment in this population.

Beta-thalassemia, a type of inherited blood disorder, reduces the levels of normal hemoglobin and red blood cells via mutations in the beta-globin subunit; this can ultimately cause the delivery of oxygen throughout the body to be at insufficient levels. The subsequently low levels of red blood cells can result in a number of health problems, such as dizziness, weakness, fatigue, bone abnormalities, and other more serious complications.

The most severe form of the condition, transfusion-dependent beta-thalassemia, often requires the standard course of treatment as being life-long red blood cell transfusions. Such transfusions can be associated with varying health conditions related to problems caused by the excessive buildup of iron in the body, such as in the heart, liver, and other organs .

Counter to the standard life-long course of treatment, betibeglogene autotemcel would be a one-time, single dose gene therapy product. Each dose would be customized to the patient using their bone marrow stem cells that are genetically modified to create functional beta-globin, a hemoglobin component, in the patient’s body.

In 2 multicenter clinical studies that included adult and pediatric patients with beta-thalassemia requiring regular transfusions, investigators established the safety and efficacy of betibeglogene autotemcel. The investigators established the efficacy of the drug based on the achievement of transfusion independence, which is the point at which the patient maintains a pre-determined level of hemoglobin without needing any red blood cell transfusions for at least 12 months. Of 41 patients who had been administered betibeglogene autotemcel, 89% were able to achieve transfusion independence.

“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”

During the trial, the investigators observed that the most common adverse effects associated with betibeglogene autotemcel included 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).

While there is a potential risk of blood cancer associated with betibeglogene autotemcel, no cases were observed during the investigation of the drug. However, patients who receive betibeglogene autotemcel should have their blood monitored for at least 15 years following the treatment for any evidence of cancer. Additionally, it is also recommended that patients be monitored for thrombocytopenia, bleeding, and hypersensitivity reactions during betibeglogene autotemcel administration as well.

Reference

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 17, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-treat-adult-and-pediatric-patients-beta-thalassemia-who