Pioneering gene editing therapy for thalassemia approved for UK use

A world-first treatment for the most severe blood disorders using a Nobel prize winning gene-editing tool has been approved for use in the UK for patients over 12. Casgevy is a pioneering gene therapy that targets sickle-cell disease and transfusion dependent beta- thalassaemia , a hereditary condition more common in the UAE and the rest of the region than elsewhere. By using the revolutionary gene-editing CRISPR tool, for which its inventors were awarded the Nobel Prize in Chemistry in 2020, precise regions of human DNA can be corrected to treat serious diseases. It has become an indispensable resource in biological research, and was used to develop Casgevy, which modifies errors in genes for haemoglobin used by red blood cells to transport oxygen around the body. Casgevy works by editing the faulty gene in a patient’s bone marrow stem cells, so the body begins to produce functioning haemoglobin. Stem cells are extracted from bone marrow, edited in a laboratory and then infused back into the patient, with potential life-long results. After rigorous assessment, the treatment has been authorised by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), and could lead to further applications of CRISPR to develop similar treatments. “The MHRA will continue to closely monitor the safety and effectiveness of Casgevy, through real-world safety data and post-authorisation safety studies being carried out by the manufacturer,” said Julian Beach, interim executive director of healthcare quality and access at the MHRA. In clinical trials for sickle-cell disease, 45 patients are receiving the treatment in the UK. Of those, 29 have been involved in the treatment long enough to record significant results, with 97 per cent free of severe pain for at least 12 months post treatment. In a parallel trial, 54 beta-thalassaemia patients received Casgevy, with 42 taking it long term. Of those, 93 per cent did not require a usual blood transfusion for at least a year after the treatment, with the remaining 7 per cent of patients reporting a more than 70 per cent reduction in the need for a red blood cell transfusion. Sickle cell disease and b-thalassemia are painful, life-long conditions that in some cases can be fatal. Previously, the only permanent treatment option was to have a bone marrow transplant – which must come from a closely matched donor and carries a risk of rejection. People with beta-thalassaemia can develop severe anaemia, and often require a blood transfusion every three to five weeks, and lifelong injections and medication. It is a major health challenge in the Emirates and other parts of the region, with traditional marriage practices and consanguinity thought to contribute to high incidence rates. Mandatory premarital screening has been publicly funded since 2008, with neonatal screening in place since 1995. Genetic counselling is also available to couples identified as carriers, and to their families. According to research published by the University of Oxford, severe forms of thalassemia can cost an estimated Dh131,156 ($35,713) annually per patient, of which life-long and regular iron chelation therapy and regular blood transfusions constitute the majority of medical expenses. In February, clinical trials in Abu Dhabi got under way to test the safety and effectiveness of Mitapivat. The drug is already approved in the US and EU to manage pyruvate kinase deficiency, a similar condition that causes blood cells to deteriorate faster than usual. It has also shown promise in treating thalassaemia. The breakthrough success of Casgevy in the UK, could pave the way for further investigations into its effectiveness in the UAE, and bring hope to families coping with lifelong debilitating blood disorders. “There are limited medicines currently available to patients,” said John James, chief executive of the UK Sickle Cell Society. “I welcome this new treatment that has been judged safe and effective, which has the potential to significantly improve the quality of life for so many.”

Pioneering gene editing therapy for thalassemia approved for UK use

Casgevy is world’s first gene therapy targeting blood disorders using gene-clipping tool