Key Facts:
The Food and Drug Administration (FDA) approved a new treatment on Friday based on Crispr gene-editing technology for the treatment of sickle cell disease. This is the first time a treatment using this technology has received official approval in the United States, with hopes that this revolutionary tool will emerge from the lab and transform the field of medicine.
Background Information:
The FDA approved Casgevy for treating sickle cell disease in patients aged 12 years and older. Casgevy is produced by Vertex Pharmaceuticals, based in Boston, and Crispr Therapeutics in Switzerland, and is also known as exagamglogene autotemcel or exa-cel. This treatment is the first of its kind to use the powerful Crispr gene-editing tool to target the underlying cause of sickle cell disease.
Information about Sickle Cell Disease:
Sickle cell disease, also known as sickle cell anemia, is a group of inherited blood disorders that affect the body’s ability to produce functional hemoglobin, the protein responsible for transporting oxygen in red blood cells throughout the body. The genetic mutation responsible for sickle cell disease causes red blood cells to crinkle or take on a sickle shape, which can block blood vessels and hinder the delivery of oxygen throughout the body, leading to serious and potentially life-threatening problems such as severe pain, stroke, and organ damage.
Clinical Trials and Treatment:
Clinical trials for the treatment indicate that Casgevy, administered as a one-time treatment, can help alleviate symptoms and provide hope for a cure for a condition that has largely outpaced scientists except for the risky alternative of bone marrow transplants. It is estimated that around 100,000 people in the United States suffer from sickle cell disease, most of whom are Black.
Interesting Fact:
Although Casgevy edits DNA inside the human body, it does not actually fix the root cause of sickle cell disease. Rather than repairing the mutation responsible for producing the faulty hemoglobin, Casgevy targets the genes responsible for making a different type of hemoglobin that is typically switched off shortly after birth. This genetic solution stimulates the production of fetal hemoglobin typically suppressed in the body, helping red blood cells maintain their healthy, disc-shaped form. Although the treatment is given once, the entire process can take months and involves laboratory work to modify blood cells and recovery in the hospital after the modified cells are injected into the patients.
Main Background:
The FDA’s decision comes weeks after the UK’s medical agency approved exa-cel, the first Crispr-based treatment to receive regulatory approval in the world. At that time, Vertex’s CEO, Reshma Kewalramani, celebrated the approval saying it was a “historic day in science and medicine.” The journey of Crispr to the clinic has been rapid since its discovery and use in the lab. This tool, derived from bacterial immune systems, was discovered more than a decade ago and earned the Nobel Prize in Chemistry in 2020. By allowing scientists to manipulate DNA with precision – often described as genetic scissors – it has been highlighted as a potentially transformative tool in the life sciences, with possible applications ranging from transferring traits such as disease resistance across species, to correcting defective genes in medical practice, and even reviving extinct animals. Despite the clear benefits, experts warn that the technology is a double-edged sword. For example, while Crispr can be used to render a virus harmless to humans, it can also be used to design a more virulent pathogen. Additionally, the ability to modify human DNA raises the prospect of enhancements rather than repairs to genes, opening the door to slippery slopes toward elitism.
What
Must Follow:
The medical agency in the UK has approved the use of Casgevy for the treatment of beta thalassemia (β-thalassemia) in addition to sickle cell disease. Beta thalassemia is another hereditary blood disorder characterized by hemoglobin production. The FDA also considers treatment for beta thalassemia and is expected to make a decision on it by the end of March next year.
What We Don’t Know:
When considering the treatment, FDA advisors – who supported the therapy – expressed confidence in the drug’s effectiveness and benefits but cautioned against the theoretical implications of human genetic modifications. Due to the novelty of the technology and its clinical application, experts warn that there could be unintended outcomes with unknown consequences, for example, if the treatment leads to genetic modifications elsewhere (known as off-target modifications). The British medical agency confirmed that it found no significant safety concerns and said that the safety of Casgevy will be closely monitored after approval.
Further Reading:
The first gene-editing treatment using Crispr has been approved in the UK (Forbes)
Is Crispr technology safe? Gene editing received its first scrutiny from the FDA (Nature)
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