01 May 2024

A new gene editing therapy for sickle cell disease and β-thalassaemia showed benefits for more than 90% of patients, according to the final results of the first clinical trials.

Exagamglogene autotemcel (exa-cel) received regulatory approval in the UK and approval from the USA Food and Drugs Agency in December.

Researchers have now published in the New England Journal of Medicine the results of open label clinical trials involving nearly 100 patients. The treatment uses CRISPR to edit DNA within the cells of patients, to reactivate production of foetal haemoglobin and ameliorate symptoms. The trials were undertaken in the USA and several European countries.

In the CLIMB SCD-121 study, 44 patients with sickle cell disease received exa-cel. Of the 30 patients who had sufficient follow-up data, not one needed hospital treatment during the study period, while all but one remained free of vaso-occlusive crises, the researchers report.

In the CLIMB THAL-111 study, 52 patients with transfusion-dependant β-thalassaemia received exa-cel. Of the 35 with sufficient follow-up data, 32 needed no transfusions during the study period, the researchers report.

Dr Stephan Grupp, one of the leaders of the sickle cell study, and medical director of the Cell and Gene Therapy Laboratory at the Children’s Hospital of Philadelphia, USA, said: “In this clinical trial, sickle cell patients who were having significant issues with their disease began to see their problems resolve within months and improve their quality of life significantly.”

In December, authorising the use of the treatment, the UK Medicines and Health Regulatory Agency (MHRA) announced similar results from trials in the UK. However last month the National Institute for Health and Care Excellence (NICE) announced draft proposals to refuse approval for the treatment on the NHS on the basis of it being not cost-effective. Charities are campaigning to overturn the decision.

At the time, Helen Knight, director of medicines evaluation at NICE, said: “The appraisal committee considered that exa-cel could represent a potential cure for some people with sickle cell disease, freeing people from the burden of vaso-occlusive crises as well as addressing NICE’s aim of reducing health inequalities associated with the condition.

“As such, and acknowledging the limitations with the evidence, NICE is willing to accept higher than the usual maximum for assessing cost-effectiveness.”


Frangoul H, Locatelli F, Sharma A, Bhatia M, Mapara M, Molinari L, Wall D, Liem RI, Telfer P, Shah AJ, Cavazzana M, Corbacioglu S, Rondelli D, Meisel R, Dedeken L, Lobitz S, de Montalembert M, Steinberg MH, Walters MC, Eckrich MJ, Imren S, Bower L, Simard C, Zhou W, Xuan F, Morrow PK, Hobbs WE, Grupp SA; for the CLIMB SCD-121 Study Group. (2024) “Exagamglogene Autotemcel for Severe Sickle Cell Disease.” New England Journal of Medicine, 24 April 2024, doi: 10.1056/NEJMoa2309676.


Locatelli F, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, de la Fuente J, Shah AJ, Carpenter B, Kwiatkowski JL, Mapara M, Liem RI, Cappellini MD, Algeri M, Kattamis A, Sheth S, Grupp S, Handgretinger R, Kohli P, Shi D, Ross L, Bobruff Y, Simard C, Zhang L, Morrow PK, Hobbs WE, Frangoul H; CLIMB THAL-111 Study Group. (2024) “Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia.” New England Journal of Medicine, 24 April 2024, doi: 10.1056/NEJMoa2309673.


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