Exagamglogene autotemcel for treating severe sickle cell disease in people 12 years and over

  • Technology appraisal guidance
  • TA1044
  • Published: 
Download guidance (PDF)

1 Recommendations

1.1

Exagamglogene autotemcel (exa‑cel) is recommended with managed access as an option for treating sickle cell disease (SCD) in people 12 years and over:

  • who have:

    • recurrent vaso-occlusive crises (VOCs) and

    • a βS/βS, βS/β+ or βS/β0 genotype and

  • when haematopoietic stem cell transplant (HSCT) is suitable, but a human leukocyte antigen-matched related haematopoietic stem cell donor is not available.

    It is only recommended:

  • for people who have had at least 2 VOCs (as defined in section 3.4) per year during the 2 previous years and

  • if the conditions in the managed access agreement for exa‑cel are followed.

Why the committee made these recommendations

Standard care for SCD includes hydroxycarbamide, blood transfusions and iron chelation therapy to remove excess iron in the blood. People who are well enough can have an HSCT if available. When an HSCT is suitable but there is no available human leukocyte antigen-matched donor, exa‑cel is a possible cure.

In SCD, damaged red blood cells can block blood flow to parts of the body, depriving them of oxygen and causing severe pain. This is often called a VOC. Evidence from a clinical trial suggests that exa‑cel can result in people not having VOCs. But this is uncertain because exa‑cel was not compared with anything else, the number of people in the trial was small and it was not clear how well it works in the long term.

As well as the uncertainties in the clinical evidence, there are several issues and uncertainties with the economic modelling. These include:

  • the model structure

  • the survival and quality-of-life outcomes used for people having exa‑cel and standard care

  • how long exa-cel's treatment effect lasts

  • how often people withdraw from exa‑cel treatment before having the infusion

  • the characteristics at the start of treatment of people having exa‑cel and

  • the frequency of complications.

But, more uncertainty and a higher cost-effectiveness estimate than NICE normally considers to be a cost-effective use of NHS resources is acceptable because of:

  • the health inequalities experienced by people with SCD

  • the innovative nature of the technology and

  • its uncaptured benefits for the quality of life of carers.

Taking this into account, exa‑cel has the potential to be cost effective compared with standard care. But the cost-effectiveness estimates are highly uncertain. This is because of the uncertainty about exa‑cel's long-term effects and its impact on quality of life, and about the outcomes for people having standard care. Some of the most likely cost-effectiveness estimates are higher than what NICE normally considers an acceptable use of NHS resources, even when accounting for exa‑cel's potential impact on health inequalities. So, exa‑cel is not recommended for routine use in the NHS.

Collecting more data through a managed access agreement may resolve some uncertainty in the evidence. So, exa‑cel is recommended for use with managed access.