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MHRA Approves Gene-editing Therapy for Two Blood Disorders

A new treatment for sickle cell disease and transfusion-dependent β-thalassemia has been authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) in a world first that aims to relieve the symptoms of the blood disorders.

Casgevy (exagamglogene autotemcel, Vertex) is based on the innovative gene-editing tool CRISPR, which won its inventors the Nobel Prize in Chemistry in 2020. 

The treatment edits the faulty gene in a patient's bone marrow stem cells enabling the production of functioning haemoglobin, with the results having the potential to be life-long.

In the UK, approximately 15,000 people have sickle cell disorder, and 813 people have transfusion-dependent beta-thalassaemia major.

John James, chief executive of the Sickle Cell Society, emphasised that sickle cell disorder was an "incredibly debilitating" condition, and caused significant pain for the people who lived with it, and potentially led to early mortality. In the UK, the mean age of death for people living with sickle cell disease is around 40, whilst for those with transfusion-dependent β-thalassemia, the mean age of death is around 55.

Julian Beach, interim executive director of healthcare quality and access at the MHRA, stressed that to date, a bone marrow transplant — which must come from a closely matched donor and carries a risk of rejection — had been the only permanent treatment option.

Sickle cell disorder had "very limited" treatment options, according to Dr Sara Trompeter, a consultant haematologist at University College Hospitals London and NHS Blood and Transplant, and clinical lead Sickle Cell Diverse Data Genomics England. "Whilst curative treatments may not be suitable for all, gene therapy offers a real chance of cure for those who are not eligible for bone marrow transplants," she said.

Disease Symptoms Relieved For Most

There are an estimated 2000 patients eligible for Casgevy in the UK, according to the manufacturer. The treatment is indicated for sickle cell disease in patients with recurrent vaso-occlusive crises who had the βS/βS, βS/β+ or βS/β0 genotype, and for the treatment of transfusion dependent beta thalassemia, in patients 12 years of age and older for whom haematopoietic stem cell transplantation was appropriate and a human leukocyte antigen-matched related hematopoietic stem cell donor is not available.

The innovative gene-editing treatment was found in trials to restore healthy haemoglobin production in the majority of participants with sickle cell disease and transfusion-dependent β -thalassaemia, relieving disease symptoms. 

In the clinical trial for sickle cell disease, analysis of 29 patients who had received Casgevy showed that 97% (28) were free of severe pain crises for at least 12 months after treatment. 

Of the 42 patients with transfusion-dependent β-thalassemia, 93% (39) hadn't needed a red blood cell transfusion for at least 12 months after treatment, with the remaining three patients experiencing a 70% reduction in the need for red cell transfusions. 

Side effects from treatment were similar to those associated with autologous stem cell transplants and included, nausea, fatigue, fever, and increased risk of infection. The MHRA said that no significant safety concerns had been identified during the trials, but this continued to be monitored.

A "Positive Moment in History"

"This authorisation offers a new option for eligible patients who are waiting for innovative therapies, and I look forward to patients having access to this therapy as quickly as possible," said Josu de la Fuente, professor of practice (cellular & gene therapy) at Imperial College London, and consultant haematologist at Imperial College Healthcare NHS Trust.

Mr James emphasised the scarcity of available medicines for patients, highlighting the value of a new treatment deemed safe and efficient. He welcomed its potential to greatly enhance the quality of life for many individuals.

Simon Waddington, professor of gene therapy at University College London (UCL), explained to the Science Media Centre that current treatments could have "very unpleasant" side effects, and described the approval as a "tremendous" advance. 

The future of life-changing cures resided in CRISPR based technology, explained Dr Helen O'Neill, programme director, reproductive science and women's health at University College London (UCL). 

"The use of the word 'cure' in relation to sickle cell disease or β-thalassemia has, up until now, been incompatible," she pointed out, making today's authorisation by the MHRA "a positive moment in history."