UK drugs regulator first to approve gene-editing therapy

UK's drugs regulator, Medicines and Healthcare products Regulatory Agency (MHRA), has approved a groundbreaking treatment for two debilitating lifelong blood disorders, that works by “editing” the gene that causes them. The MHRA is the first in the world to approve Casgevy (exagamglogene autotemcel), also known as exa-cel, to be used to treat sickle cell disease and beta thalassemia. Both conditions are genetic or inherited and can be fatal.

Sickle cell disease (SCD) is the most common inherited blood disorder that affects your red blood cells. In SCD, a protein called hemoglobin, located within red blood cells, is abnormal. Hemoglobin is important. It’s the molecule that carries oxygen in your blood and throughout your body.

Beta thalassemia is a blood disorder that reduces the production of hemoglobin. In people with beta thalassemia, low levels of hemoglobin reduce oxygen levels in the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.

Casgevy is a genetically modified autologous CD34+ cell enriched population containing human hematopoietic stem and progenitor cells edited?ex vivo?by CRISPR/Cas9 at the erythroid-specific enhancer region of the?BCL11A?gene.

The approval by the Medicines and Healthcare products Regulatory Agency (MHRA) follows promising results from clinical trials that tested the one-time treatment, which is administered by intravenous infusion and was developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland. The clinical trial for sickle-cell disease followed 29 out of 45 participants long enough to draw interim results. Casgevy completely "cured" 28 of those people of debilitating episodes of pain for at least one year AFTER treatment. In the clinical trial for β-thalassaemia, which is conventionally treated with blood transfusions once a month, 54 participants received Casgevy and 42 participated long enough to provide interim results. For at least one year AFTER treatment, 39 (out of the 42) participants did not need a red-blood-cell transfusion while the remaining 3 (out of the 42) had their need for blood transfusions reduced by over 70%.

The MHRA said: “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 lifelong.”

The companies did not announce a price for the gene therapy but it is expected to carry a price tag in the millions of dollars. Cost is not the only hurdle, as Casgevy requires patients to undergo a “pre-conditioning” chemotherapy to clear out space in the bone marrow for the edited stem cells to establish themselves and this can cause a range of side effects such as painful mouth sores and the risk of infertility. The US Food and Drug Administration is considering approval of Casgevy for sickle-cell disease. The European Medicines Agency is also reviewing the treatment for both diseases.