A groundbreaking potential cure for sickle cell disease is on the horizon, offering new hope for individuals suffering from this painful inherited blood disorder. Currently, the only cure for sickle cell disease involves a bone marrow transplant, but this new therapy targets the genetic root of the disease.
On Tuesday, a panel of advisors to the Food and Drug Administration (FDA) will conduct a thorough review of a gene therapy designed to combat this hereditary condition, which predominantly affects Black people in the United States. The advisors will evaluate various aspects, including the need for further research into any unintended consequences associated with the treatment.
If granted approval by the FDA, this therapy will mark a historic milestone as the first gene therapy on the U.S. market based on CRISPR, the gene-editing tool that earned its inventors the Nobel Prize in 2020. The FDA is expected to make its decision regarding this treatment in early December, with another sickle cell gene therapy under consideration later in the same month.
Dr. Allison King, who specializes in the care of children and young adults with sickle cell disease, expressed enthusiasm for the potential new treatments. She noted, “Anything that can help relieve somebody with this condition of the pain and the multiple health complications is amazing.”
Sickle cell disease affects the shape of hemoglobin, the protein responsible for carrying oxygen within red blood cells. A genetic mutation results in these cells taking on a crescent shape, leading to blockages in blood flow, excruciating pain, organ damage, stroke, and other complications. This condition impacts millions worldwide, including approximately 100,000 individuals in the U.S., with higher prevalence among populations from regions where malaria is or was common, such as Africa and India, and certain ethnic groups.
Current treatments for sickle cell disease include medications and blood transfusions, with bone marrow transplants being the sole permanent solution, albeit with the added complexity of finding a suitable donor. The new gene therapy, known as “exa-cel,” developed by Vertex Pharmaceuticals and CRISPR Therapeutics, does not require a donor and involves permanent alterations to a patient’s blood cells’ DNA.
The therapy aims to encourage the body to revert to producing fetal hemoglobin, naturally present at birth but replaced by a defective adult form in individuals with sickle cell disease. This involves extracting stem cells from the patient’s blood, using CRISPR to modify the gene responsible for the transition, and then reintroducing the altered stem cells.
Although the treatment has been tested on a limited number of patients thus far, early results are promising. A pivotal study involved 46 patients, and among those with at least 18 months of follow-up, the vast majority were free of pain crises for over a year, and none required hospitalization for pain crises during that period. The treatment was described as “transformative” with a strong safety profile.
The FDA is, however, seeking guidance from an external panel of gene therapy experts to address a lingering concern associated with CRISPR technology—possible “off-target effects,” unintended and unwanted alterations to a person’s genome. The agency is keen to ensure that the company’s research adequately assesses these risks or whether additional studies are necessary. While not binding, the FDA often follows the advice of such panels.
If approved for the market, the company has proposed post-approval safety studies, comprehensive product labeling outlining potential risks, and ongoing research. Another gene therapy for sickle cell disease, developed by Bluebird Bio, is also under FDA consideration and offers a different approach. This therapy aims to insert modified genes into red blood cells to produce “anti-sickling” hemoglobin, preventing or reversing cell deformation.
While prices for these therapies have not been disclosed, an institute report suggests that costs up to around $2 million would be cost-effective when compared to the considerable expenses associated with current sickle cell treatments, which amount to approximately $1.6 million for women and $1.7 million for men from birth to age 65.
Dr. King recognizes that these new treatments may come at a high cost but emphasizes the significant value they offer in improving the lives of individuals suffering from sickle cell disease, reducing pain, and decreasing hospitalization stays.
Gary P Hernal started college at UP Diliman and received his BA in Economics from San Sebastian College, Manila, and Masters in Information Systems Management from Keller Graduate School of Management of DeVry University in Oak Brook, IL. He has 25 years of copy editing and management experience at Thomson West, a subsidiary of Thomson Reuters.
