In a landmark decision, the Food and Drug Administration has approved the first gene therapies to treat people with sickle cell disease – a crippling condition that leaves patients in life-altering pain.
On Friday, the government gave the green light to Casgevy and Lyfgenia for the treatment of sickle cell disease in patients aged 12 years and older.
Casgevy is the first FDA-approved treatment using a new type of gene-editing technology called CRISPR. Lyfgenia uses conventional gene therapy – not gene editing – to treat the condition.
Sickle cell disease is the umbrella term for a group of hereditary conditions that seriously affect the shape and function of red blood cells. It affects 100,000 Americans, most of whom are black.
These newly approved therapies could offer hope to Americans with the condition, which was only approved for treatment through a bone marrow transplant, an invasive procedure for which most patients are not eligible.
Dr. Reshma Kewalramani, CEO and president of Vertex Pharmaceuticals, one of the companies behind Casgevy, said: “The FDA approval of CASGEVY is momentous: it is the first CRISPR-based gene editing therapy to be approved in the US.”
While the news brings hope for sickle cell patients, there are concerns in the medical community that the therapies will be difficult to access due to the expected high costs and limited hospitals that can administer them.
Patients with sickle cell disease, of which there are about 100,000 in the U.S., do not properly produce hemoglobin — a substance in red blood cells that transport oxygen throughout the body. As a result, their red blood cells become stiff and form a crescent shape (pictured) instead of a disk, which can cause them to die and become stuck in blood vessels.
Casgevy, made by Boston-based Vertex Pharmaceuticals (pictured) and Crispr Therapeutics in Switzerland, works by editing the defective gene behind sickle cell disease in a patient's bone marrow stem cells so that the body produces functioning hemoglobin.
Casgevy's genome editing technology has been approved to treat sickle cell patients with recurrent vaso-occlusive crises – a complication of the condition that occurs when sickle-shaped red blood cells block blood flow, leaving tissues severely deprived of oxygen.
About 16,000 patients experience this 'flare-up' of sickle cell disease.
But because of Casgevy's advanced technology, Vertex says “specialized experience in stem cell transplantation is required” and only a handful of hospitals are authorized to perform the treatment.
The company is working with hospitals in Boston, Los Angeles, Dallas and San Antonio, Texas, Columbus, Ohio, Chicago, Nashville and Washington, DC, and plans to engage with more facilities in the coming weeks.
Another obstacle to accessing the treatment: the expected multi-million dollar price tag.
Casgevy, developed in collaboration with Switzerland-based Crispr Therapeutics, was recently approved in Britain for the treatment of sickle cell disease, but it is expected to cost the British government about £1 million ($1.25 million) per patient.
The FDA's approval of Casgevy means that for the first time, patients can have access to a one-time therapy that has the potential to cure their condition, Dr. Kewalramani said.
Unlike Casgevy, Lyfgenia, developed by Bluebird Bio, uses gene therapy exclusively. It is approved for the treatment of patients 12 years and older with sickle cell disease and a history of vaso-occlusive events.
This one-time treatment genetically modifies a patient's blood stem cells to use gene therapy to produce hemoglobin, the protein in red blood cells responsible for delivering oxygen throughout the body, which functions like normal hemoglobin in healthy people.
Blood cells containing the healthy hemoglobin have a lower risk of sickling and blocking blood flow.
After modification, the stem cells are then delivered to the sickle cell patient.
Dr. Julie Kanter, a researcher working on Lyfgenia, called the therapy 'transformative'
And Regina Hartfield, president and CEO of the Sickle Cell Disease Association of America Inc., said it could change the lives of people and families affected by sickle cell disease.”
In someone without sickle cell disease, red blood cells – produced by stem cells in the bone marrow – are round, hollow discs that bend and bend easily.
However, in people with the condition, defective stem cells produce red blood cells that are crescent-shaped. These cells are stiff, unable to penetrate smaller blood vessels, and are prone to blockages that deprive parts of the body of oxygen, leading to immense pain and organ damage.
Until now, a bone marrow transplant was the only approved treatment for the condition. A transplant is a procedure in which healthy blood-forming stem cells are transplanted from a healthy donor to replace bone marrow in the patient that is not producing enough healthy cells.
Stem cells are the 'raw materials' of the body, or cells that can develop into many different specialized cell types. They can be used to repair damaged tissue, and researchers believe stem cell therapies could one day treat conditions like Alzheimer's disease and paralysis.
In most cases of a bone marrow transplant, the donor is a brother or sister, but even a brother or sister has only a one in four chance of being a match for the patient. And often transplants are not performed because of the risks, including the transplanted cells attacking other cells in the recipient's body, which can be life-threatening.
There are more than 30 FDA-approved gene therapies used to treat various types of cancer and the blood disease hemophilia. However, many are largely inaccessible due to the high cost.
The gene therapy uses the innovative gene editing tool CRISPR, the process known as 'genetic scissors' that allows scientists to make precise changes to DNA.
Its inventors received the Nobel Prize in 2020.
The therapy works by editing the defective HBB gene, which causes sickle cell disease, so that the body can produce properly functioning hemoglobin.
To do this, stem cells are taken from a patient's bone marrow and processed in a laboratory using the 'scissors', which precisely switches off the defective gene.
Stem cells are then injected back into the patient, who may have to spend a month or more in the hospital while the treated cells start making healthy red blood cells.
Scientists believe the results have the potential to be lifelong.
An ongoing study of the drug to date shows that 97 percent of sickle cell patients were free of severe pain for at least a year after treatment.
Dr. Samarth Kulkarni, chairman and CEO of CRISPR Therapeutics, also called Casgevy “transformative.”
The CEO added, “This approval of the first-ever drug using CRISPR gene editing is breathtaking.”