EMA’s human medicines committee (CHMP) has endorsed findings of a review which concluded that there is no evidence Zynteglo causes a blood cancer known as acute myeloid leukaemia (AML).

Zynteglo, a gene therapy for the blood disorder beta thalassaemia, uses a viral vector (or modified virus) to deliver a working gene into the patient’s blood cells.

The review considered two cases of AML in patients treated with an investigational medicine, bb1111, in a clinical trial for sickle cell disease. Although there have been no reports of AML with Zynteglo, both medicines use the same viral vector and there was a concern that the vector may be implicated in the development of the cancer (insertional oncogenesis).

The review by EMA’s safety committee (PRAC) supported by experts from the Committee for Advanced Therapies (CAT) found that the viral vector was unlikely to be the cause. In one of the patients, the viral vector was not present in the cancer cells, and in the other patient it was present at a site (VAMP4) that does not appear to be involved in cancer development.

After examining all the evidence, it was clear that more plausible explanations for the AML cases included the conditioning treatment the patients received to clear out bone marrow cells and the higher risk of blood cancer in people with sickle cell disease.

Patients having Zynteglo treatment for beta thalassaemia also need conditioning treatment to clear out their bone marrow cells before receiving Zynteglo. Healthcare professionals should therefore explicitly inform patients receiving Zynteglo of the increased risk of blood cancers from medicines used in conditioning treatments.

The CHMP has agreed on an update of recommendations for monitoring patients. Healthcare professionals should now check their patients for signs of blood cancers at least once a year for 15 years.

The CHMP concluded that the benefits of Zynteglo continue to outweigh its risks. As for all medicines, the EMA will monitor any new data on its safety and update advice for patients and healthcare professionals when necessary.

Published on: 23 July 2021