NICE approves groundbreaking one-off gene therapy for severe sickle cell disease

Some people in England with severe sickle cell disease will be among the first to benefit from the world's first CRISPR gene editing technology, NICE has said in final draft guidance published today (31 January 2025). 

NICE's independent appraisal committee has approved the use of gene editing therapy exagamglogene autotemcel (exa-cel) for use in the NHS in England, providing a potential cure for some people with severe sickle cell disease (SCD).  

It will be made available under a managed access scheme for treating severe SCD in some people 12 years and over with recurrent vaso-occlusive crises (VOCs) who have a βS/βS, βS/β+ or βS/β0 genotype. 

The committee heard from a patient expert who described how the severe and distressing lifelong disease had affected them and that treatment with exa-cel had made them "healthier, fitter and stronger than at any point in my life before". 

Costing £1,651,000 per course at its list price1, treatment with exa-cel (also called Casgevy and made by Vertex) involves collecting the person's blood stem cells. These are then edited in a lab to produce high levels of fetal haemoglobin in red blood cells after they are returned to the body in a single infusion. The functional fetal haemoglobin compensates for the non-functional haemoglobin caused by SCD.  

As exa-cel involves people receiving their own edited cells, they have no risk of their body rejecting them. 

Dr Samantha Roberts, NICE chief executive, said: “Exa-cel could represent a potential cure for some people with severe sickle cell disease, freeing people from the burden of complications as well as addressing NICE's aim of reducing health inequalities associated with the condition and getting the best care to patients fast.” 

Funmi Dasaolu, who has sickle cell disease and was nominated by charity Anthony Nolan to tell her story to the NICE committee, said: "The approval of exa-cel today marks a significant shift in the treatment landscape of sickle cell disease in the UK. It is the beginning of re-addressing the inequalities in care experienced by so many with the condition. It provides much needed hope and will undoubtedly radically transform the lives of those living with this genetic blood disorder.” 

There are very few treatments to stop symptoms of SCD and those that are available often have intolerable side effects. Currently the only curative treatment for people with SCD is a donor stem cell transplant. Exa-cel will now be an option when a stem cell transplant is suitable but no matched donor can be found.    

The committee took into account exa-cel's potential impact on health inequalities (SCD is more common in people from African, Caribbean, Middle Eastern or South Asian family backgrounds), its innovative nature and the uncaptured benefits of the treatment for the quality of life of carers by allowing more uncertainty in the evidence and a higher cost-effectiveness estimate than NICE normally considers to be value for money for the NHS.  

Recognising the life-long and severe nature of the disease it was agreed that the 1.2 severity weighting could be applied 

More data will be collected while patients receive the treatment on the NHS before NICE evaluates the medicine again. Collecting more data through a managed access agreement may resolve some uncertainty in the evidence, particularly about how long the benefits of treatment with exa-cel last and whether people return to full health or near full health with exa-cel or continue to have any SCD-related complications.  

NICE already recommends exa-cel with managed access as an option for treating transfusion-dependent beta-thalassaemia in people 12 years and over.  

References 

1 The company has a commercial arrangement. This makes exa‑cel available to the NHS with a discount. 

1. The final draft guidance for exagamglogene autotemcel for treating sickle cell disease is available on the NICE website (from 00:01, 31 January 2025) at: https://www.nice.org.uk/guidance/indevelopment/gid-ta11249/documents.  An embargoed copy is available here: ID4016 exa-cel final draft guidance.docx
   
   
2. Today's announcement follows a managed access agreement (MAA) between NHS England and company Vertex to allow further data collection for exa-cel for treating severe sickle cell disease. Details of the MAA are available on the NICE website (from 00:01, 31 January 2025) at: https://www.nice.org.uk/guidance/indevelopment/gid-ta11249/documents.
   
   
3. It is estimated that around 1,700 people with severe SCD could be eligible for exa-cel. However, the complexity and intensity of the treatment will mean that only a smaller proportion will complete the treatment pathway. NHS England estimates this number to be around 50 per year. This is similar to the number of children and adults with sickle cell disease who receive a stem cell transplant on the NHS each year. 
   
   
4. In SCD, a gene mutation causes red blood cells to become irreversibly sickle shaped. These cells are then broken down in a process called haemolysis. In many people with SCD, their red blood cells are destroyed faster than they can be made, leading to low haemoglobin levels and a condition called haemolytic anaemia. This causes many of the symptoms of SCD, including pain, fatigue, weakness, tachycardia (heart rhythm disorder), dizziness and confusion.
    
5. In the longer term SCD can cause organ damage, strokes, sight loss and other symptoms, which substantially affect quality of life.  
   
   
6. Life expectancy for people with SCD is reduced, particularly for people with severe disease. People with SCD are also more likely to develop other illnesses such as stroke, kidney failure and heart conditions.
   
   
7. According to a recent Sickle Cell Society survey, in the past 2 years 45% of people with SCD had more than 8 VOCs, 66% needed emergency care and support at least 2 to 3 times, and 24% spent 1 to 2 weeks in hospital. 
   
   
8. Usual treatment for SCD includes ensuring adequate hydration, preventing infections, regulating body temperature and treating pain, with or without hydroxycarbamide. Regular blood transfusions and iron chelation therapy may also be considered.
   
   
9. For people who are fit enough and have an available matched-related donor, allogeneic haematopoietic stem cell transplants (HSCTs) are a potentially curative treatment option. In this appraisal clinical experts highlighted that only around 15% of people with SCD have suitable donors available and graft versus host disease can develop as a result of these HSCTs.
   
   
10. The clinical effectiveness evidence for exa-cel was based on 30 people, who were followed up for an average of 20.1 months. The independent Evidence Assessment Group for this appraisal said that the trial suggests that exa-cel is very effective for a limited number of people in the short term. It highlighted that the assumption of a lifetime effectiveness is currently based on clinical opinion, so robust long-term evidence needs to be collected from more people who are followed up for longer.