Regulators on Friday approved two gene therapies for sickle cell disease that doctors hope can cure the painful, inherited blood disorder that mainly affects black people in the US.
The Food and Drug Administration said the one-time treatments can be used for patients 12 years and older with severe forms of the disease. One, made by Vertex Pharmaceuticals and CRISPR Therapeutics, is the first approved therapy based on CRISPR, the gene-editing tool that won its inventors the 2020 Nobel Prize. The other is made by Bluebird Bio and works differently.
"Sickle cell disease is a rare, debilitating and life-threatening blood disorder with a significant unmet need," said Dr. Nicole Verdun of the FDA in a statement announcing the approvals. seriously disturbed by the disease."
The two gene therapies are the first approved in the US for sickle cell disease. The FDA has previously approved 15 gene therapies for other conditions. Some have list prices in the millions of dollars, and that includes sickle cell therapies.
In the US, an estimated 100,000 people have sickle cell disease and about a fifth of them have the severe form. Sickle cell disease is most common among black people, and nationally, 1 in 365 black babies are born with the disease. Scientists believe that being a carrier of sickle cell disease helps protect against severe malaria, making the disease more common in areas where mosquitoes are common, such as Africa, or in people whose ancestors lived in those places.
The disease affects hemoglobin, the protein in red blood cells that transports oxygen. A genetic mutation causes the cells to become sickle or crescent shaped, which can block blood flow and cause excruciating pain, organ damage, stroke and other problems.
Current treatments include medications and blood transfusions. The only permanent solution is a bone marrow transplant, which must come from a closely matched donor and carries a risk of rejection.
The gene therapies, which permanently change the DNA in the patient's blood cells, do not require a donor. The goal of the Vertex therapy, called Casgevy, is to help the body return to producing a fetal form of hemoglobin that is present at birth - it is the adult form that is defective in people with sickle cell disease. CRISPR is used to switch off a gene in stem cells collected from the patient.
Bluebird's treatment, called Lyfgenia, aims to add copies of a modified gene, which helps red blood cells produce 'anti-sickle cell' hemoglobin that prevents or reverses misshapen cells.
When patients receive the treatments, stem cells are removed from their blood and sent to a laboratory. Before they get the changed cells back, they must undergo chemotherapy. The process requires at least two hospitalizations, one of which lasts four to six weeks.
Still, many patients say they would consider gene therapy given the severity of the disease.
Jalen Matthews of Louisville, Kentucky, was diagnosed with sickle cell disease at birth and had her first episode of pain at age nine. Three years later, the disease led to a stroke in the spinal cord, leaving her with some paralysis in her left arm and leg.
"I had to learn to walk again, to feed myself, to dress myself, to basically do everything again," says Matthews, now 26.
Today, she keeps her sickle cell disease at bay with transfusions every two months, replacing five units of her blood with healthy cells. She said gene therapy might be a better option and she plans to ask her doctor about it.
"This one-time form of healing is desperately needed," says Matthews.
The FDA approval is the first for Bluebird's treatment; Vertex has previously been approved in Britain and Bahrain.
Studies testing the therapies suggest they work well. Of the 31 people treated with adequate follow-up in the pivotal Vertex study, 29 were free of pain crises for at least a year. In the Bluebird study, 28 of 32 patients had no severe pain or organ damage between six and 18 months after therapy.
But doctors point out that there are possible side effects and long-term results are unknown. For both, the necessary chemotherapy carries risks, such as infertility, hair loss and vulnerability to serious infections.
Blood cancer has occurred with Bluebird therapy, so the FDA said the label will include a "black box warning" about that risk. With the Vertex therapy, some scientists worry that CRISPR carries the possibility of "off-target effects," which are unexpected changes in a person's genome.
"It is important to be cautious and optimistic about this therapy, but also know that there is still not much experience with it," said Dr. Benjamin Watkins, director of the pediatric stem cell and cell therapy program at Children's Hospital New Orleans. .
Doctors said they don't expect every medical center to offer the gene therapies because it requires so much equipment and coordination among medical specialists. They also don't expect that many people will immediately look for them. Watkins said some may want to wait until more people get the treatments.
Experts also warned that cost could be a hurdle. The list price for Bluebird Bio is $3.1 million and for Vertex $2.2 million. What patients can afford depends on insurance coverage and other factors. To help cover costs, the U.S. Centers for Medicare and Medicaid Services announced a plan that aims to create partnerships with state Medicaid agencies and pharmaceutical companies.
But ultimately, gene therapy "could be transformative and actually change the landscape of sickle cell disease," says Dr. Monica Bhatia, who treats children with the disease at NewYork-Presbyterian.
Matthews, who volunteers with the Sickle Cell Association of Kentuckiana, said she is hopeful the treatments will have a big impact.
"It's a blessing," she said. "It will really benefit all of us in the sickle cell community."
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