On 23 July 2021, the European Medicines Agency (EMA) announced that its Committee for Medicinal Products for Human Use (CHMP) has endorsed findings of a review by the Pharmacovigilance Risk Assessment Committee (PRAC) which concluded that there is no evidence Zynteglo causes an 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 EMA review by 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 medicines used in the conditioning treatment the patients received to clear out bone marrow cells and the higher risk of haematological malignancy 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 haematological malignancy 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 haematological malignancy at least once a year for 15 years. The previous recommendation was for healthcare professionals to check for signs of haematological malignancy once a year.

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. 

Zynteglo is a one-time treatment for a blood disorder known as beta thalassaemia in patients 12 years and older who require regular blood transfusions.

To make Zynteglo, the stem cells taken from the patient’s blood are modified by a virus that carries working copies of the beta-globin gene into the cells. When these modified cells are given back to the patient, they are transported in the bloodstream to the bone marrow where they start to make healthy red blood cells that produce beta-globin. The effects of Zynteglo are expected to last for the patient’s lifetime.

Zynteglo was granted conditional marketing authorisation in May 2019. The conditional authorisation means that there is more evidence to come about the medicine, which the company will provide. EMA regularly reviews new information that becomes available.

The review of Zynteglo was initiated on 18 February 2021 at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.

The review was first carried out by the PRAC, the committee responsible for the evaluation of safety issues for human medicines, which worked closely with experts from the CAT.

The PRAC recommendations were sent to the CAT, which adopted a draft opinion on 16 July 2021 in line with the PRAC recommendations, and subsequently to the CHMP, responsible for questions concerning medicines for human use. On 22 July 2021, the CHMP adopted the Agency’s final opinion taking into account the draft opinion of the CAT. The CHMP opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.