The Food and Drug Administration approved a new therapy for sickle cell disease based on CRISPR gene editing on Friday, marking the first time a treatment based on the technology has received regulatory approval in the United States, amid hopes that the revolutionary tool will emerge from the lab and transform medicine.
Casgevy, a Crispr-based therapeutic, has been approved by the FDA for the treatment of sickle cell disease in individuals aged 12 and up.
Casgevy, also known as exagamglogene autotemcel, or exa-cel, is a first-of-its-kind medication developed by Boston-based Vertex Pharmaceuticals and Switzerland’s Crispr Therapeutics that uses the potent gene-editing tool Crispr to address the fundamental cause of sickle cell disease.
Sickle cell disease, also called sickle cell anemia, is a group of inherited blood disorders that affect the body’s ability to produce functioning hemoglobin, the protein in red blood cells responsible for carrying oxygen around the body.
The genetic mutation responsible for sickle cell disease means red blood cells fold, or sickle, where they can block blood vessels and prevent oxygen from being ferried around the body, triggering serious and potentially fatal problems like severe pain, stroke, and organ damage
Casgevy, which is given as a one-time treatment, has been shown in clinical studies to help ease symptoms and offer hope of a solution for the ailment, which has mainly eluded doctors beyond risky bone marrow transplants.
Approximately, More than 100,000 people in the United States and 20 million people globally are affected by the illness.
Casgevy, which changes DNA within the human body, does not address the underlying cause of sickle cell disease. Casgevy targets genes involved in manufacturing an alternative type of hemoglobin, which is generally switched off shortly after birth, rather than the mutation responsible for incorrect hemoglobin production. This genetic workaround causes the body to produce normally suppressed fetal hemoglobin, which aids blood cells in maintaining their healthy, disc-like shape. While the treatment is only given once, the entire process can take months, including laboratory work to change blood cells and hospital rehabilitation once the modified cells are pumped into patients.
The FDA’s decision comes only weeks after Britain’s medical regulator approved exa-cel, making it the world’s first agency to do so. Reshma Kewalramani, CEO and President of Vertex at the time, called the clearance “a historic day in science and medicine.” Crispr’s path to the clinic has been brisk, beginning with its discovery and application in the lab. The technique, drawn from bacterial immune systems, was discovered a little more than a decade ago and earned its creators the Nobel Prize in Chemistry in 2020. By allowing scientists to modify DNA with precision—the technology is commonly described as a pair of genetic scissors—it was quickly praised as a tool with transformational potential across the life sciences, with possible uses ranging from transferring features for genetic research to transferring traits for drug development.
While Crispr might be used to create a virus that is safe for people, it could also be utilized to create a more virulent infection. The ability to modify human DNA also opens the possibility of mutations aimed to improve rather than correct, raising the threat of a slippery slope toward eugenics.
Casgevy has been approved by the United Kingdom’s medical authorities to treat beta-thalassemia (-thalassemia) and sickle cell disease. Another genetic blood illness defined by hemoglobin synthesis is beta-thalassemia. The FDA is also investigating beta-thalassemia therapy and is expected to make a judgment by the end of March next year.
When considering the treatment, FDA experts indicated they were confident in the drug’s efficacy and benefit but were concerned about the potential repercussions of human genetic changes. Given the technology’s novelty and application in the clinic, scientists caution that there may be unforeseen consequences, such as if the therapy causes genetic mutations elsewhere (known as off-target alterations). The panel was emphatic, however, that the therapy’s apparent clinical value should not be swamped by theoretical considerations. The British regulator stated that there were no substantial safety issues and that Casgevy’s safety would be closely monitored after clearance.
