CRISPR therapies show promise for sickle cell and thalassaemia in younger children

Data on the effectiveness and safety of Casgevy gene therapy in children aged five to 11 years has been reported.

Casgevy, a CRISPR-based genome-editing-treatment, has successfully treated children aged five to 11 years for the treatment of two blood disorders – sickle cell disease and transfusion-dependent beta-thalassaemia. Casgevy has already been authorised at over 65 centres worldwide for people 12 years of age and older with a severe form of either disease and for whom a stem cell transplant donor can not be found. The National Institute for Health and Care Excellence approved funding for the treatment of beta-thalassaemia in August 2024 (see BioNews 1251) and for the treatment of sickle cell disease in January 2025 (see BioNews 1275). Now, researchers have reported results from two Phase 3 clinical trials, one for each disorder, at the American Society of Haematology's annual meeting in Orlando, Florida.

'These results – the first clinical data ever presented on any genetic therapy for children ages five to 11 years with [sickle cell disease] – again demonstrate the transformative potential of Casgevy,' said Dr Carmen Bozic, chief medical officer at Vertex Pharmaceuticals in Boston, Massachusetts, which developed the drug in partnership with CRISPR Therapeutics in Zug, Switzerland.

Eleven children aged between five and 11 with sickle cell disease were treated with Casgevy in the clinical trial. All four children who have completed at least one year post-treatment were reported to be free of vaso-occlusive crises, a painful organ injury occurring when blood cells cause blockages, common to sickle cell disease patients.

Thirteen children aged between five and 11 with transfusion-dependent beta-thalassaemia were also treated with Casgevy. All six children who have completed at least one year post-treatment were reported to have not required any further blood transfusions. One child died from pneumonia and multi-organ failure due to severe veno-occlusive disease related to the pre-transplant chemotherapy treatment, and not the gene therapy itself.

'A 100 percent success rate is rare in anything that we do,' said Dr Haydar Frangoul, who gave the presentation, confirming that 'All younger patients with sufficient follow-up met the primary endpoint of being transfusion independent in those with beta thalassaemia and free of vaso-occlusive crises for those with sickle cell disease.'

Sickle cell disease and beta-thalassaemia are caused by different mutations in a single gene
that codes for haemoglobin, an essential blood molecule that helps red blood cells carry oxygen around the body. Currently, the main treatment for both is a stem cell transplant, but it can be difficult to find a donor.

Casgevy is the brand name for exagamglogene autotemcel (exa-cel), formerly known as CTX001. During treatment, blood stem cells are taken from the patient, which are then edited outside the body. Specifically, CRISPR/Cas9 genome editing is used to precisely cut a strand of DNA at a specific site on the faulty adult haemoglobin gene. Modification of this gene results in the reactivation of fetal haemoglobin production, enabling the production of a functioning haemoglobin gene when the edited stem cells are transplanted back into the patients.

However, patients must first undergo chemotherapy and radiotherapy to wipe out their immune system before it can be rebuilt through a single-dose infusion of Casgevy containing their own modified stem cells.

Vertex plans to initiate global regulatory filings for the use of Casgevy in treating children aged between five and 11 with sickle cell disease or transfusion-dependent beta-thalassaemia in the first half of 2026.