NEW YORK – The UK National Institute for Health and Care Excellence on Friday issued a final draft guidance recommending that the National Health Service (NHS) make Vertex Pharmaceuticals and CRISPR Therapeutics' sickle cell disease gene therapy Casgevy (exagamglogene autotemcel) available to patients in England.
NICE recommended that the one-time gene therapy, which is the first commercialized drug to use CRISPR gene editing, be available under a managed access agreement for patients at least 12 years of age with severe sickle cell disease who have recurrent vaso-occlusive crises (VOCs) and who are eligible for a stem cell transplant but don't have a donor. Under a managed access program, patients can, for a time, access promising treatments that are not yet routinely recommended due to uncertain clinical or cost considerations. During this process, sponsors can collect additional data on the clinical and cost impact of the treatment.
NICE last year did not recommend Casgevy for sickle cell disease and asked for additional data on the product's effectiveness and the duration of treatment benefit before making its final recommendation. NICE at the time said Vertex should submit an updated managed access proposal to the agency incorporating plans for such data collection.
NICE will again evaluate whether to make Casgevy permanently available through NHS England after these data are collected.
In making its final decision, NICE's independent appraisal committee considered Casgevy's potential impact on health inequalities, as sickle cell disease is more common in people with African, Caribbean, Middle Eastern, and South Asian ancestries, and the possible benefits of the treatment on quality of life for patients and caregivers.
As a result, the committee allowed for "more uncertainty in the evidence and a higher cost-effectiveness estimate than NICE normally considers to be value for money for the NHS," NICE said in a statement Friday. In addition, the lifelong and severe disease has few other treatment options available.
"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," Samantha Roberts, NICE chief executive, said in a statement.
The primary clinical evidence for Casgevy is from the single-arm, open-label Phase I/II/III CLIMB SCD-121 trial and the Phase III CLIMB-131 trial, in which patients will be monitored for up to 15 years. Twenty-eight of 29 patients who had at least 16 months of follow-up data in these studies had no severe VOCs for at least a year after treatment.
An independent evidence assessment group for NICE questioned the generalizability of results from the clinical trials and the model structure that Vertex used to estimate cost-effectiveness. In addition, data on durability were based on 30 patients who were followed on average for about 20 months, so long-term evidence still is needed to establish lifelong benefit, the group said.
Casgevy carries a list price of nearly £1.7 million ($2.05 million); however, the sponsors are making the treatment available to NHS England at an undisclosed discount.
NICE last year recommended Casgevy as a treatment for transfusion-dependent beta-thalassemia. Casgevy was approved in the US for sickle cell disease in 2023 and for transfusion-dependent beta-thalassemia last year, and has received conditional marketing authorization in the EU for both indications, as well as approvals in other countries.