NICE positive for exa-cel (exagamglogene autotemcel) to treat transfusion-dependent beta-thalassaemia for managed access but not routine use

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

only if the conditions in the managed access agreement for exa-cel are followed.

Why the committee made this recommendation

Standard care for beta-thalassaemia includes blood transfusions and iron chelation therapy to remove excess iron in the blood. If people who have regular blood transfusions are well enough, an HSCT is an option. Exa-cel is a possible cure when an HSCT is suitable but there is no human leukocyte antigen-matched stem cell donor.

Clinical trial evidence shows that exa-cel removes the need for blood transfusions in most people. But, in the trial, people were only followed up for a relatively short time, and exa-cel was not compared with any other treatment. Evidence from an indirect comparison shows that exa-cel reduces the need for transfusions compared with standard care. But the number of transfusions that most people have as part of standard care needs confirming.

As well as the uncertainties in the clinical evidence, there are several issues with the economic modelling, including:

the model structure;

i.how long the treatment effect with exa-cel lasts

ii.how often people withdraw from exa-cel treatment before the infusion takes place

iiithe survival and quality-of-life outcomes used for people having exa-cel and standard care

iv.the frequency of complications.

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 in exa-cel's long-term effects and impact on quality of life, and in the outcomes for people on 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.-term effects and impact on quality of life, and in the outcomes for people on 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(exa-cel) is recommended with managed access as an option for treating transfusion-dependent beta-thalassaemia in people 12 years and over:

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

ii. only if the conditions in the managed access agreement for exa?cel are followed.

Why the committee made this recommendation

Standard care for beta-thalassaemia includes blood transfusions and iron chelation therapy to remove excess iron in the blood. If people who have regular blood transfusions are well enough, an HSCT is an option. Exa-cel is a possible cure when an HSCT is suitable but there is no human leukocyte antigen-matched stem cell donor.

Clinical trial evidence shows that exa-cel removes the need for blood transfusions in most people. But, in the trial, people were only followed up for a relatively short time, and exa-cel was not compared with any other treatment. Evidence from an indirect comparison shows that exa-cel reduces the need for transfusions compared with standard care. But the number of transfusions that most people have as part of standard care needs confirming.

As well as the uncertainties in the clinical evidence, there are several issues with the economic modelling, including:

the model structure;

i. how long the treatment effect with exa-cel lasts

ii. how often people withdraw from exa-cel treatment before the infusion takes place

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

iv. the frequency of complications.

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 in exa-cel's long-term effects and impact on quality of life, and in the outcomes for people on 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.-term effects and impact on quality of life, and in the outcomes for people on 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