In a world first, medical regulators in the UK have approved a gene therapy that aims to cure two blood disorders – sickle cell disease and beta thalassemia – the first such treatment to be licensed using the gene-editing tool CRISPR, for which its discoverers were awarded the Nobel prize in 2020.
The authorisation of the therapy, from Vertex Pharmaceuticals and CRISPR Therapeutics, is itself not a surprise. Clinical trials have shown the one-time treatment enabled many sickle cell patients to live free of debilitating pain crises and relieved thalassemia patients of needing regular blood transfusions, raising hopes that they have been effectively cured.
But it also stands as a major achievement, coming just more than a decade after the first and seminal lab experiments that showed CRISPR’s potential as a gene-editing tool were published.
Both of the inherited blood conditions – sickle cell disease and beta thalassemia – are triggered by errors in the gene for haemoglobin.
BBC News reports that people with sickle cell disease produce unusually shaped red blood cells that can cause problems because they do not live as long as healthy blood cells and can block blood vessels, causing pain and life-threatening infections.
Beta thalassaemia means the person does not produce enough haemoglobin, used by red blood cells to carry oxygen around the body. Patients with beta thalassemia often need a blood transfusion every few weeks of their lives.
How it works
Gene-editing allows the precise manipulation of DNA. The treatment involves removing bone marrow stem cells from the blood.
In a laboratory, the gene-editing tool CRISPR uses molecular scissors to make precise cuts in the DNA of the cells, thus disabling the faulty gene. The modified cells are infused back, allowing the body to start producing functioning haemoglobin.
In trials, 28 out of 29 sickle cell patients were free of severe pain and 39 of 42 beta thalassemia patients no longer needed blood transfusions for at least a year. It's hoped it could be a permanent fix.
Trials are continuing in the UK, US, France, Germany and Italy.
Professor Josu de la Fuente from Imperial College Healthcare NHS Trust is leading the UK trials in adults and children. He told the BBC he was delighted the drug had been licensed: “This is the kind of technology you read about in science fiction books and never think would be reality – here we are in my professional life being able to be part of the story and deliver it to patients.”
Around 15 000 people in the UK have sickle cell disease, most with an African or Caribbean family background. Almost 300 babies are born in the UK with sickle cell disease each year.
More than 1 000 people in the UK are affected by thalassemia, mainly those of Mediterranean, southeast Asian and Middle Eastern origin.
“Both sickle cell disease and beta thalassemia are painful, life-long conditions that in some cases can be fatal,” said Julian Beach, interim executive director of healthcare quality and access at the Medicines and Healthcare Products Regulatory Agency (MHRA).
“To date, a bone marrow transplant – which must come from a closely matched donor and carries a risk of rejection – has been the only permanent treatment option.”
But now, the first-of-its-kind gene-editing treatment called Casgevy has been authorised by the MHRA.
In trials, it was found to restore healthy haemoglobin production in most participants with sickle-cell disease and transfusion-dependent beta thalassaemia, relieving the symptoms of disease.
John James OBE, chief executive of the Sickle Cell Society said: “Sickle cell disorder is an incredibly debilitating condition, causing significant pain for the people who live with it and potentially leading to early mortality.
“There are limited medicines currently available, so the news that a new treatment has been judged safe and effective will have the potential to significantly improve the quality of life for so many.”
No price has yet been set for Casgevy, but the one off treatment is likely to cost £1m or more, which could be deemed too high a price for the NHS to bear. It will now be up to the health assessment body NICE to determine if it is cost-effective.
In April, a US think tank, ICER, said the drug would be cost effective if it were priced at no more than £1.5m.
For Casgevy, the drug is a personalised one-off treatment made from tweaking the patient’s own cells – that makes it expensive and time-consuming. Add in the cost of research and development – there are just two labs one in the US and the other in the UK – currently producing the drug.
Boston-based pharma company Vertex will want its product used as widely as possible so will need to set a price that health services everywhere are prepared to pay.
BBC article – Casgevy: UK approves gene-editing drug for sickle cell (Open access)
See more from MedicalBrief archives:
FDA advisers debate sickle cell gene therapy safety
Gene therapy: A game changer for those with sickle-cell disease
Sickle cell disease 11 times more deadly than thought – global study