UK approves world’s 1st gene therapy to treat sickle-cell, thalassemia

The UK has approved the world's first gene therapy to treat blood disorders sickle-cell disease and thalassemia using the gene-editing tool CRISPR, which won its inventors the Nobel Prize in 2020.

So far, a bone marrow transplant -- which must come from a closely matched donor and carries a risk of rejection -- has been the only permanent treatment option.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) authorised the new treatment called Casgevy for patients with sickle-cell disease and transfusion-dependent beta-thalassemia aged 12 and over.

Both sickle cell disease and beta-thalassemia are genetic conditions caused by errors in the genes for haemoglobin, which is used by red blood cells to carry oxygen around the body.

Casgevy is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin.

To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long.

In people with sickle cell disease, the genetic error can lead to attacks of very severe pain, serious and life-threatening infections, and anaemia (whereby your body has difficulty carrying oxygen). Among beta-thalassaemia patients, it can lead to severe anaemia. Patients often need a blood transfusion every 3 to 5 weeks, and injections and medicines throughout their lives.

“Both sickle cell disease and beta-thalassemia are painful, life-long conditions that in some cases can be fatal,” said Julian Beach, Interim Executive Director of Healthcare Quality and Access at the MHRA, in a statement.

“We have authorised an innovative and first-of-its-kind gene-editing treatment called Casgevy, which in trials has been found to restore healthy haemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent beta-thalassaemia, relieving the symptoms of disease,” she added.

Casgevy’s approval for sickle-cell disease was based on a clinical trial of 29 patients, of which 28 (97 per cent) were free of severe pain crises for at least 12 months after treatment.

Of the 42 patients in the clinical trial for transfusion-dependent beta-thalassemia, 39 (93 per cent) did not need a red blood cell transfusion for at least 12 months after treatment. The remaining three had more than a 70 per cent reduction in the need for red cell transfusions.

Side effects from treatment were similar to those associated with autologous (from a person’s own cells) stem cell transplants, including (but not limited to) nausea, fatigue, fever and increased risk of infection.

No significant safety concerns were identified during the trials, the MHRA said, adding that the safety of the treatment will be analysed further.

Casgevy is currently being evaluated by the US Food and Drug Administration (FDA) and is expected to receive the agency’s approval next month.