United Kingdom approves first-ever CRISPR treatment, a cure for sickle cell disease and beta thalassemia

In a world first, U.K. regulators yesterday approved a therapy that uses the gene-editing technique CRISPR. The approach treats two inherited blood disorders, including sickle cell disease, which afflicts mostly people of African ancestry, by modifying a patient’s blood stem cells in the lab and returning them to the patient.

In sickle cell disease, a defect in the oxygen-carrying protein hemoglobin, found in red blood cells, causes the cells to form a sickled shape that clogs blood vessels, leading to severe pain and sometimes strokes and organ damage. The new treatment from the companies Vertex Pharmaceuticals and CRISPR Therapeutics is designed to replace these malfunctioning proteins with working versions encoded by a hemoglobin gene that is normally active in a developing fetus. After harvesting a patient’s blood stem cells, scientists use CRISPR to disable the genetic switch that normally turns off this fetal hemoglobin gene early in development. The cells are then reinfused into the body, where newly made hemoglobins take up the job of transporting oxygen.

In clinical trials, all but one of 29 people who have received the treatment for sickle cell started to make fetal hemoglobin and no longer had severe pain episodes; and 39 of 42 patients who received it for a related disorder, beta thalassemia, no longer needed blood transfusions to avoid severe anemia. Unlike bone marrow transplants, the one available cure for these diseases if a matching donor can be found, the infusion of a patient’s own edited cells does not pose a risk of immune system rejection.

The treatment “has the potential to significantly improve the quality of life for so many,” said an official from the United Kingdom’s Medicines and Healthcare products Regulatory Agency in a press release today. The agency approved the therapy, which the companies have called Casgevy, for patients ages 12 or older with sickle cell disease or beta thalassemia.

Regulators in other countries are likely to soon follow suit. In the United States, an advisory panel to the Food and Drug Administration (FDA) last month concluded that the benefits of the treatment for sickle cell patients far outweighed risks, such as CRISPR making off-target cuts in the wrong location in the genome. FDA is expected to approve it for sickle cell disease by 8 December; a decision by European regulators is also pending. A conventional gene therapy treatment from bluebird bio that pastes a new gene for adult hemoglobin into blood cells is also expected to receive FDA approval for sickle cell disease this month; the $2.8 million product is already on the market for beta thalassemia.

Questions will arise about whether the U.K.’s National Health Service and U.S. insurance companies will pay for the CRISPR treatment, also expected to be millions of dollars. Also clouding Casgevy’s approval is that most people with sickle cell disease live in Africa , which has few medical facilities that can offer the complex care needed to deliver the treatment. Those steps include chemotherapy to wipe out a patient’s existing blood cells and make room for the edited ones.