In 2020, scientists Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for developing the genome editing method, and three years later, the tool was licensed for the treatment of sickle cell disease and beta-thalassemia.
Both inherited blood disorders are caused by errors in the hemoglobin gene.
People with sickle cell anemia produce abnormally shaped red blood cells that do not live as long as healthy cells and can block blood vessels, causing pain and life-threatening infections. At the same time, patients with beta-thalassemia do not produce enough hemoglobin, which is used by red blood cells to carry oxygen throughout the body, and need blood transfusions every few weeks.
How the drug works
A drug for the treatment of sickle cell disease and beta-thalassemia in people aged 12+ called exagamglogen autotemcel (exa-cel, trade name Casgevy) was developed by CRISPR Therapeutics and Vertex Pharmaceuticals and has already been licensed by the British medical regulators.
It “turns off” the BCL11A gene, which normally suppresses the production of fetal hemoglobin after birth, and this form of hemoglobin replaces the defective one in an adult, taking over the functions of oxygen delivery. The purpose of the drug is to take hematopoietic stem cells from the patient’s bone marrow, edit them in the laboratory and inject them back, having previously prepared the body to accept these cells. The whole process takes several months, but should cure the patient for a long time (potentially for life).
First results
During the trials, 28 of 29 patients with sickle cell disease did not experience severe pain, and 39 of 42 patients with beta-thalassemia did not need blood transfusions for at least a year.
Tests are still ongoing in the UK, the US, France, Germany, and Italy.
According to the BBC, about 15,000 people in the UK have been diagnosed with sickle cell disease (most belong to African or Caribbean families). Every year, nearly 300 children with sickle cell disease are born in the country. More than 1,000 people in the UK suffer from beta-thalassemia, mostly from the Mediterranean, Southeast Asia and the Middle East.
Both sickle cell anemia and beta-thalassemia are life-long conditions that can be fatal in some cases. To date, bone marrow transplantation from a close donor (which has a risk of rejection) has been the only permanent treatment option.
How much will the therapy cost?
The high cost of Casgevy is likely to limit the drug to those who can benefit from it. The price of treatment in the UK has not yet been determined, but according to Nature, it may cost about $2 million per patient, which is in line with the price of other gene therapy methods.
“We have not set a list price for the UK at this time and are focused on working with health authorities to ensure reimbursement and access for eligible patients as soon as possible,” a Vertex Pharmaceuticals spokesperson told Nature.
Meanwhile, the U.S. Food and Drug Administration is considering approving Casgevy for the treatment of sickle cell disease; and the European Medicines Agency is reviewing the treatment for both diseases.
