by Regulators on Friday approved two gene therapies for sickle cell disease that doctors hope can cure the painful, inherited blood disorder that mostly affects black people in the US.
The Food and Drug Administration said the one-time treatments can be used for patients 12 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 Nobel Prize in 2020. The other is made by Bluebird Bio and works in a different way.
“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with a significant unmet need,” said the FDA’s Dr. Nicole Verdun in a statement announcing the approvals. greatly affect the disease.”
The two gene therapies are the first therapies approved in the United States for sickle cell. The FDA has previously okayed 15 gene therapies for other conditions. Some have list prices in the millions of dollars, and so will the sickle cell therapies.
In the United States, it is estimated that 100,000 people have sickle cell disease and about a fifth of them have the severe form. Sickle cell is most common among Black people and 1 in 365 black children are born with the disease nationally. Scientists believe that this helps protect against severe malaria when you carry the sickle cell trait, so the disease occurs more often in mosquito-prone regions such as Africa or in people whose ancestors lived in those places.
The disease affects haemoglobin, the protein in red blood cells that carries oxygen. A genetic mutation causes the cells to become sickle or sickle-shaped, which can block blood flow, causing excruciating pain, organ damage, stroke and other problems.
Current treatments include medication 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.
No donor is required for the gene therapies, which permanently change DNA in the patient’s blood cells. The goal of the Vertex therapy, called Casgevy, is to help the body go back to producing the fetal form of hemoglobin that is present at birth – the adult form that is defective in people with sickle cell disease. CRISPR is used to knock out 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-sick” hemoglobin that prevents or reverses malformed 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 have to undergo chemotherapy. The process requires at least two hospitalizations, one lasting 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 at birth and had her first episode of pain at age 9. Three years later, the disease caused a spinal cord stroke that left her paralyzed in her left arm and leg.
“I had to learn how to walk again, feed myself, clothe myself, basically learn how to do everything again,” said Matthews, now 26.
Today, she keeps her sickle cell locked in with a blood transfusion every two months or so, and five units of her blood are replaced with healthy cells. She said gene therapy might be a better option and plans to ask her doctor about it.
“This type of one-time cure is very much needed,” Matthews said.
The FDA approval is the first for a Bluebird treatment; Vertex is previously authorized in Britain and Bahrain.
Studies testing the therapies suggest they work well. Of the 31 people treated in the pivotal Vertex study who had adequate follow-up, 29 were free of pain crises for at least a year. In the Bluebird study, 28 out of 32 patients had no serious pain or organ damage between six and 18 months after the therapy.
But doctors point out that there are possible side effects and the long-term results are unknown. For both, the necessary chemotherapy comes with risks such as infertility, hair loss and vulnerability to serious infection.
With Bluebird therapy, blood cancer has occurred, so the FDA said the label will include a “black box warning” about that risk. With the Vertex therapy, some scientists worry that CRISPR opens up the possibility of off-target effects, which are unexpected changes to a person’s genome.
“It’s important to be cautious and optimistic about this therapy, but also to know that there is not much experience yet,” said Dr. Benjamin Watkins, director of the pediatric stem cell and cell therapy program at Children’s Hospital. New Orleans. .
The doctors said they don’t expect every medical center to offer the gene therapies because it requires so much equipment and coordination between medical specialists. They just expect a lot of people to be looking for it right away. Watkins said some people may want to wait until more people get the treatments.
Experts also warned that cost could be an obstacle. The list price for Bluebird Bio is $3.1 million and $2.2 million for Vertex. What patients may pay will depend on insurance coverage and other factors. To help cover the cost, the US Centers for Medicare and Medicaid Services announced a plan that aims to establish partnerships with state Medicaid agencies and drug companies.
But ultimately, gene therapy “could be transformative and really change the landscape of sickle cell disease,” said 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 greatly benefit all of us in the sickle community.”
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The Associated Press Health and Science Section is supported by the Howard Hughes Medical Institute Science and Media Education Group. The AP is solely responsible for all matters.
