Currently, the sole remedy for the discomfort caused by sickle cell disease is a bone marrow transplant. However, in the near future, there may be a novel cure that targets the root cause of the disorder on a genetic level.
Advisers to the Food and Drug Administration will meet on Tuesday to assess a gene therapy aimed at treating an inherited blood disorder that disproportionately impacts Black individuals in the U.S. Among the factors they will examine is the need for further investigation into potential unexpected repercussions of the therapy.
If given the green light by the FDA, it would become the initial gene therapy in the United States utilizing CRISPR, the gene-editing technology that earned its creators the Nobel Prize in 2020.
The agency is anticipated to make a decision on the treatment in the beginning of December, prior to addressing a separate sickle cell gene therapy at the end of the month.
Dr. Allison King, a physician specializing in treating children and young adults with sickle cell disease, expressed excitement about potential new treatments.
King, a professor at Washington University School of Medicine in St. Louis, expressed that anything that can alleviate the pain and health issues experienced by individuals with this condition is remarkable. The condition is excruciating and can be described as being stabbed repeatedly.
The condition impacts the hemoglobin, which is the protein responsible for carrying oxygen in red blood cells. A change in genetic code results in the cells taking on a crescent shape, potentially obstructing blood flow and leading to severe discomfort, organ harm, stroke, and other complications.
Millions of people around the world, including about 100,000 in the U.S., have the disease. It occurs more often among people from places where malaria is or was common, like Africa and India, and is also more common in certain ethnic groups, such as people of African, Middle Eastern and Indian descent. Scientists believe being a carrier of the sickle cell trait helps protect against severe malaria.
At present, available remedies consist of medications and blood transfusions. The sole lasting resolution is a transplant of bone marrow, which necessitates a donor who is closely matched and does not have the disease; however, there is a possibility of rejection.
A donor is not necessary for the single-session gene therapy, known as “exa-cel,” developed by Vertex Pharmaceuticals and CRISPR Therapeutics. This novel method involves permanently altering the DNA of a patient’s blood cells.
The objective is to assist the body in returning to its production of fetal hemoglobin, which is normally present at birth but eventually transitions to a faulty adult form in individuals with sickle cell disease.
During the treatment, stem cells are extracted from the patient’s blood and CRISPR technology is utilized to disable the switching gene. The patient then receives medication to eliminate any remaining defective blood-producing cells, followed by the reintroduction of their modified stem cells.
According to a report from the nonprofit Institute for Clinical and Economic Review, the treatment has only been tested on a limited number of patients at this time.
On Friday, Vertex released a briefing document for the upcoming advisory committee meeting stating that 46 individuals received the treatment during the pivotal study. Out of the 30 participants who were followed up for at least 18 months, 29 remained free of pain crises for a year or more and all 30 were able to avoid hospitalization due to pain crises during that time.
The treatment was referred to as “transformational” by the company and they stated that it has a “robust safety record.”
Earlier this year, at a scientific conference, Victoria Gray from Mississippi became the first patient to try out the treatment. She talked about her lifelong struggles with excruciating pain and receiving strong painkillers and even blood transfusions. She also shared that the gene therapy made her feel like she was starting a new life.
She can now play and spend time with her children while also holding a full-time job. “My kids no longer worry about me getting sick from sickle cell disease,” she stated.
The FDA has requested a meeting with a team of gene therapy specialists to address a recurring concern in conversations about CRISPR: the potential for “off-target effects,” which are unintentional alterations to a person’s genetic makeup. The FDA seeks guidance on whether the company’s research on these effects was thorough enough to evaluate the associated risks or if further studies are necessary. Though the agency is not obligated to heed the panel’s recommendations, it typically does.
If the treatment is approved for market use, the company has suggested conducting a safety study after approval, providing product labeling that outlines potential risks, and continuing research.
The Food and Drug Administration is anticipated to make a decision on Bluebird Bio’s second gene therapy for sickle cell disease before the year ends. This treatment functions uniquely by inserting modified genes that produce “anti-sickling” hemoglobin into red blood cells, preventing or reversing the formation of misshapen cells.
No estimated costs have been disclosed by the companies for either treatment, however, according to a report from the institute, prices up to $2 million would be considered cost-effective. In contrast, recent research revealed that medical expenses for existing sickle cell treatments, from birth until age 65, total approximately $1.6 million for women and $1.7 million for men.
The St. Louis doctor, King, admitted that the cost of the new treatments would be high. However, she posed the question, “What is the value of someone experiencing relief and avoiding constant hospital visits?”
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