A groundbreaking study has shown that exagamglogene autotemcel (exa-cel), a CRISPR-based gene therapy, can effectively eliminate severe vaso-occlusive crises in patients with sickle cell disease. In a phase 3 trial involving 44 patients aged 12 to 35, exa-cel was found to provide remarkable results, with 97% of participants remaining free from these painful episodes for at least 12 consecutive months.
The therapy works by using CRISPR-Cas9 technology to edit autologous haematopoietic stem cells, reactivating fetal haemoglobin production in the body. This process aims to reduce the harmful effects of sickle cell disease, which causes red blood cells to become misshapen and block blood flow, leading to frequent and severe pain crises.
In the trial, patients underwent a myeloablative conditioning regimen with busulfan before receiving the edited cells. The results were impressive: 100% of patients were also free from hospitalisations for vaso-occlusive crises for 12 months or more. The median follow-up period was 19.3 months, and no cancers or severe safety issues were reported, with the side effects aligning with those typically seen in stem cell transplants.
These findings represent a significant leap forward for sickle cell disease treatment, offering the possibility of long-term relief from a debilitating condition. The success of exa-cel opens the door for more widespread use of CRISPR-based therapies in treating genetic disorders.
Helena Bradbury, EMJ
Reference
Frangoul H et al. Exagamglogene autotemcel for severe sickle cell disease. N Engl J Med. 2024;390:1649-62.
