The only cure for painful sickle cell disease today is a bone marrow transplant. However, there may soon be a groundbreaking new cure that targets the disorder at its genetic source.
Advisers to the Food and Drug Administration (FDA) will review a gene therapy for sickle cell disease, an inherited blood disorder that disproportionately affects Black people in the U.S. During their review, they will consider the need for further research into any unintended consequences of the treatment.
If approved by the FDA, this gene therapy will be the first on the U.S. market to utilize CRISPR, the Nobel Prize-winning gene editing tool.
The FDA is expected to make a decision on this treatment in early December, followed by the review of another sickle cell gene therapy later in the month.
Dr. Allison King, a professor at Washington University School of Medicine in St. Louis, expressed her enthusiasm for the possibility of new treatments for sickle cell disease. She acknowledged the immense pain and multiple health complications that individuals with this condition endure, and believes that any treatment that can provide relief is truly amazing.
Sickle cell disease affects the shape of red blood cells’ protein, hemoglobin, which carries oxygen. The genetic mutation responsible for the disease causes the cells to become crescent-shaped, obstructing blood flow and leading to excruciating pain, organ damage, stroke, and other serious problems.
Millions of people worldwide, including approximately 100,000 in the U.S., suffer from sickle cell disease. The disease is more prevalent in populations from regions where malaria is or was common, such as Africa and India, and among certain ethnic groups, like people of African, Middle Eastern, and Indian descent. Scientists believe that carrying the sickle cell trait helps protect against severe malaria.
Current treatments for sickle cell disease include medications and blood transfusions. However, the only permanent solution is a bone marrow transplant, which must come from a closely matched donor without the disease, and carries the risk of rejection.
In contrast, the one-time gene therapy named “exa-cel,” developed by Vertex Pharmaceuticals and CRISPR Therapeutics, does not require a donor. This innovative treatment involves permanently modifying a patient’s blood cells’ DNA.
The goal of this therapy is to stimulate the production of fetal hemoglobin, which is naturally present at birth but switches to a defective adult form in individuals with sickle cell disease.
During the treatment, stem cells are extracted from the patient’s blood and CRISPR is used to deactivate the switching gene. Patients then receive medications to eliminate other flawed blood-producing cells before reintroducing their own genetically modified stem cells.
While the treatment has been tested in a relatively small number of patients so far, the Institute for Clinical and Economic Review noted in an evidence report that 46 individuals participated in the pivotal study. Among the 30 patients with at least 18 months of follow-up, 29 remained free of pain crises for over a year, and all 30 avoided hospitalization due to pain crises during that period.
Vertex Pharmaceuticals described the treatment as “transformative” and emphasized its strong safety profile.
One of the first patients to undergo the treatment, Victoria Gray from Mississippi, shared her experience at a scientific conference. She described the unbearable pain she had endured since childhood and the high-dose pain medications and occasional blood transfusions she had received. Gray compared the day she received the gene therapy to being reborn and shared that she can now run around with her children and work a full-time job, alleviating her children’s fear of losing her to sickle cell disease.
However, the FDA has requested input from an external panel of gene therapy experts to discuss the potential “off-target effects.” These effects refer to unexpected and unwanted changes to an individual’s genome. The FDA seeks advice on whether the company’s research adequately assessed the risk of such effects or if further studies are necessary. Although the FDA is not bound by the group’s advice, it usually takes it into consideration.
If the gene therapy is allowed in the market, the company has suggested a post-approval safety study, product labeling outlining potential risks, and continued research.
Before the end of the year, the FDA is expected to decide on another gene therapy for sickle cell disease, developed by Bluebird Bio. This treatment works differently by inserting modified genes into red blood cells to produce “anti-sickling” hemoglobin that prevents or reverses the misshaping of cells.
Neither company has disclosed the potential prices for these therapies, but according to the institute report, prices up to approximately $2 million would be cost-effective. In comparison, research earlier this year estimated that medical expenses for current sickle cell treatments from birth to age 65 amount to around $1.6 million for women and $1.7 million for men.
Dr. King acknowledges that the new treatments would come at a high cost but raises the question of how much someone’s relief from pain, reduced hospitalization, and improved quality of life is worth.
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