A landmark decision by the Medicines and Healthcare products Regulatory Agency (MHRA) has made the United Kingdom the first country to authorize a therapy based on the CRISPR technology. The novel gene-editing medicine, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, is now authorized for the treatment of two inherited blood disorders, specifically, treating patients aged 12 and older who suffer from sickle cell disease or transfusion-dependent beta thalassemia. Known as exagamglogene autotemcel, or exa-cel, the medicine will be sold under the brand name Casgevy.[link]
Both disorders in question are the results of genes that code errors for hemoglobin – the oxygen-carrying proteins found on red blood cells. Sickle cell disease is characterized by abnormally crescent-shaped red blood cells and can lead to severe complications. Beta thalassemia, on the other hand, is marked by extremely low levels of hemoglobin leading to severe anemia.
Casgevy operates by extracting a patient’s stem cells from the bone marrow. These cells are then edited using CRISPR to produce high levels of fetal hemoglobin. The stem cells, once modified, are inserted back into the patient’s body, replacing the existing cells producing faulty hemoglobin.
The efficacy of the new therapy has been evident in the trail results. In a trial focused on sickle cell disease patients, 28 out of 29 patients were immune to severe pain crises for at least 12 months post-treatment. For beta thalassemia, 39 out of 42 patients didn’t require a red blood cell transfusion for at least a year following the treatment.
The therapy comes with a few side effects such as fever, nausea, fatigue, and a high risk of infections similar to the problems associated with other autologous stem cell transplant procedures.
The MHRA decision is conditional with an initial validity of one year. It is subject to renewal as long as ongoing reviews of real-world data and continued post-marketing studies offer a positive prognosis for the therapy [link]. Vertex Pharmaceuticals and CRISPR Therapeutics, partners since 2015, have not yet disclosed the price for Casgevy, but it is estimated that the U.K. hosts around 2000 patients that are eligible for the treatment.
This approval precedes upcoming regulatory decisions in the U.S. Last month, the FDA advisory committee backed the CRISPR-editing therapy. By December 8, the FDA will make its decision on the application of Casgevy for sickle cell disease, and by March 30, 2024, for beta thalassemia.