UK first to approve CRISPR gene therapy for sickle cell and beta-thalassaemia

A CRISPR-based genome-editing-treatment for two blood disorders has been authorised by the UK medicines regulator.

The UK has become the first country in the world to license a drug that uses the genome-editing approach CRISPR. The treatment, called Casgevy, was approved by the Medicines and Healthcare products Regulatory Agency for the treatment of sickle cell disease and transfusion-dependent beta-thalassemia in patients 12 years of age and older.

'This is a world-first and a significant moment for researchers, clinicians and, most of all, people with sickle-cell disease and beta thalassaemia' Professor Josu de la Fuente, chief national investigator for the UK clinical trials and consultant haematologist at Imperial College Healthcare NHS Trust, London, said. 'These are inherited blood disorders which have a huge impact on people's lives... This authorisation offers a new option for eligible patients who are waiting for innovative therapies'.

Sickle cell disease and beta-thalassaemia are caused by different mutations in a single gene that codes for haemoglobin, an essential blood molecule that helps red blood cells carry oxygen around the body.

The therapy involves taking a patient's own blood stem cells, called haematopoietic stem cells, and editing them outside the body. CRISPR/Cas9 genome editing is used to precisely cut a strand of DNA at a specific site on a gene that normally disables the production of fetal haemoglobin after birth. In the edited cells the fetal haemoglobin gene can be transcribed again, enabling the production of a functioning haemoglobin. The edited stem cells are then transplanted back into the patients, who are then able to produce the functioning blood molecule.

Vertex Pharmaceuticals in Boston, Massachusetts, developed the drug, formerly known as CTX001, in partnership with CRISPR Therapeutics in Zug, Switzerland. The drug has been previously shown to be effective in early clinical trials (see BioNews 1108 and 1052).

Now, two global clinical trials of Casgevy achieved their primary outcomes: 28 of 29 sickle-cell patients were free of severe pain and 39 of 42 beta-thalassaemia patients no longer needed blood transfusions, for at least a year. The remaining three had their need for blood transfusions reduced by over 70 percent.

Professor Dame Kay Davies, Dr Lee's Professor of Anatomy, University of Oxford, said: 'This is a landmark approval which opens the door for further applications of CRISPR therapies in the future for the potential cure of many genetic diseases. The challenge is that these therapies will be very expensive so a way of making these more accessible globally is key.'

The cost of Casgevy has not yet been established in the UK. The National Institute for Health and Care Excellence (NICE) has approved other gene therapies for use within the NHS, not using the CRISPR approach, for conditions such as metachromatic leukodystrophy (see BioNews 1179) and spinal muscular atrophy (BioNews 1098). Both of these have at a list price of around US$2 million per patient, but the NHS negotiated a confidential discount.

NICE is currently evaluating Casgevy (under its previous name CTX001) for use in both beta thalassaemia and sickle cell, and intends to publish findings in March and April 2024 respectively.

In October, an advisory committee for the US Food and Drug Administration (FDA) met to review the safety of the therapy, whose generic name is exa-cel. The FDA will make a decision by 8 December 2023 on whether to approve the therapy for use in the USA (see BioNews 1124). The European Medicines Agency is also reviewing the therapy.