First Cell-Based Gene Therapy for Beta-Thalassaemia Receives FDA Approval

On 17 August 2022, the FDA (US Food and Drug Administration) approved betibeglogene autotemcel (Zynteglo), the first cell-based gene therapy for adults and children with beta-thalassaemia who require regular red blood cell transfusions.

This approval is a major advance in beta-thalassaemia treatment, particularly for those needing ongoing red blood cell transfusions, and represents the most significant treatment step yet for this serious disease.

Previously, in 2019, luspatercept-aamt (Reblozyl) became the first medicine to receive FDA approval for anaemia in adults with beta-thalassaemia requiring blood transfusions. 

What Is Beta-Thalassaemia?

In beta-thalassaemia, mutations in the beta-globin subunit reduce normal haemoglobin and red blood cells, leading to inadequate oxygen delivery to the body. It is an inherited blood disorder.

Beta-thalassaemia is a cause of the low blood count medically called “anaemia”. Reduced red blood cell levels can cause dizziness, weakness, fatigue, bone abnormalities and more serious complications.

Beta-thalassaemia is a preventable blood disorder inherited from parents. It is a major public health concern in Mediterranean countries, including Türkiye. Although carrier detection, genetic counselling and prenatal diagnosis can prevent it, at least 365,000 children with thalassaemia are born and treated worldwide each year. Türkiye has around 1,300,000 carriers and about 4,500 patients.

Beta-thalassaemia is severe and, if treatment is not maintained properly, substantially shortens life and greatly impairs quality of life. Treatment is difficult and very costly, at around 10,000 dollars per patient annually. Preventing affected births is therefore important, and the government also supports the necessary preventive measures.

Transfusion-dependent beta-thalassaemia, the most severe form, usually requires lifelong red blood cell transfusions as standard treatment. These regular transfusions can themselves cause complications from excess iron accumulation, including problems affecting the heart, liver and other organs.

Studies Supporting FDA Approval

Zynteglo’s safety and efficacy were established in two multicentre trials involving adults and children with beta-thalassaemia requiring regular transfusions. Efficacy was based on transfusion independence: maintaining a predefined haemoglobin level without red blood cell transfusions for at least 12 months.

Among 41 patients receiving Zynteglo, 89% no longer depended on transfusions.

The most common adverse effects associated with Zynteglo include reduced platelets and other blood cells, mucositis, febrile neutropenia, vomiting, fever, hair loss, nosebleeds, abdominal and musculoskeletal pain, cough, headache, diarrhoea, rash, constipation, nausea, reduced appetite, pigmentation changes and itching. 

The treatment carries a potential blood cancer risk, although no cases of secondary cancer have been seen so far in patients receiving Zynteglo. Patients should be monitored for evidence of cancer for at least 15 years. They should also be monitored for hypersensitivity during administration and for thrombocytopenia and bleeding.

Developed using genetic engineering, this cell-based gene therapy is currently approved and available only in the United States. Its reported cost is 2.8 million dollars for 1 patient.