UK approves CRISPR gene therapy for children aged five and over

Children aged five and older with severe sickle cell disease or transfusion-dependent beta-thalassaemia can now receive cell-based gene therapy Casgevy after the UK extended its authorisation to include eligible younger children.

Casgevy, a CRISPR genome-editing treatment, was first approved in November 2023 for patients aged 12 and older (see BioNews 1216). Now, the Medicines and Healthcare products Regulatory Agency (MHRA) has authorised its use in eligible children aged five and older. This may allow children to be treated before long-term organ damage from these disorders occurs and potentially reduce the impact of the conditions on their education and social lives.

'This approval means this innovative genome-editing treatment can now be used in eligible children from the age of five, extending this treatment option to younger patients. It is based on careful assessment of the available evidence on the treatment's safety, quality and effectiveness,' said Julian Beach, interim executive director, operations at MHRA. 'As with all medicines, we will continue to closely monitor the safety and effectiveness of Casgevy.'

An updated managed access agreement from the National Institute for Health and Care Excellence (NICE), together with a reimbursement agreement with NHS England, means eligible patients based in England can now access treatment through the NHS. Casgevy's manufacturer, Vertex, said it is working with health authorities in Scotland, Wales and Northern Ireland to extend access for eligible patients.

Sickle cell disease and transfusion-dependent beta-thalassaemia are serious, lifelong inherited blood disorders caused by different mutations in a single gene that encodes haemoglobin. Haemoglobin is required by red blood cells to carry oxygen around the body.

Severe sickle cell disease can cause pain, life-threatening infections and anaemia, while beta-thalassaemia can cause severe anaemia requiring regular blood transfusions. Both conditions can lead to lasting complications that arise early in life. Treatment varies between the conditions, but may involve regular blood transfusions and medication. In severe cases, donor stem cell transplants may be considered for some patients.

Casgevy uses the patient's own cells, avoiding some risks associated with donor transplants. Clinicians collect the patient's stem cells and edit them in a laboratory before infusing them back into the patient following conditioning chemotherapy, which prepares the bone marrow to receive the modified cells.

Casgevy works by editing a regulatory region of the BCL11A gene, increasing production of fetal haemoglobin. This type of haemoglobin can compensate for the defective haemoglobin associated with sickle cell disease and beta-thalassaemia. The patient is then monitored while the treated stem cells establish themselves in the bone marrow and begin producing red blood cells containing increased levels of fetal haemoglobin.

Professor Josu de la Fuente, consultant paediatric haematologist at Imperial College Healthcare NHS Trust, said: 'Today's approval is an important advance and offers new hope to eligible children and their families. It enables us to consider younger children for treatment earlier, before disease-related complications lead to lasting organ damage.'

Separately, a 15-year-old girl became the first patient in the UK to complete treatment with Casgevy for sickle cell disease at Royal Manchester Children's Hospital. She received treatment under the original authorisation for patients aged 12 and over, rather than the newly extended approval for younger children.