FDA Approves First CRISPR Therapy for the Treatment of Sickle Cell Disease in the U.S.

A ground-breaking CRISPR-based therapy is now available for patients with sickle cell disease in the U.S.

The U.S. Food and Drug Administration approved the gene-editing therapy on December 8th for use in patients aged 12 and older. Named as 'Casgevy', this treatment represents hope for those with harsh forms of the painful blood disorder, sickle cell disease. Furthermore, it is the world's first therapy to use genetic modification applied via the Nobel Prize-winning method known as CRISPR/Cas9. On the same day, another gene therapy for sickle cell disease, 'Lyfgenia', developed by biotech firm bluebird bio, also gained approval.

According to David Altshuler, Chief Scientific Officer at Boston-based Vertex Pharmaceuticals, the approval for the first CRISPR-based medicine is thrilling. Vertex Pharmaceuticals developed the medicine in conjunction with CRISPR Therapeutics. Altshuler finds it more inspiring that the drug fills a treatment gap for typically underserved patients.

About 100,000 people in the U.S., predominantly Black or Latino, suffer from sickle cell disease. Caused by a genetic defect in hemoglobin, the oxygen-carrying protein in red blood cells, the condition results in inflexible sickled blood cells that block blood flow and generate severe pain. People with serious forms of the disease can require hospitalization several times each year.

Kerry Morrone, a pediatric hematologist at Albert Einstein College of Medicine in New York City, says this new therapy could be a “new lease on life” for sickle cell patients and provide relief from symptoms.

At an FDA advisory committee meeting in October, several individuals who participated in the clinical trials for Casgevy described their life-changing experiences. These included the first trial participant, Victoria Gray, who described that following treatment, the debilitating pain was gone and she was able to enjoy time with her family.

Existing treatments for sickle cell disease, such as hydroxyurea and bone marrow transplants, have limitations. Casgevy works like a transplant but uses the patient's own cells. Using CRISPR, the treatment modifies the genetic structure of bone marrow cells that create blood cells. The modified cells produce fetal hemoglobin, which prevents red blood cells from sickling and blocking blood vessels.

The process involves initial chemotherapy to eradicate existing bone marrow cells, followed by editing of new cells in a lab. These new cells are then reintroduced to the patient's body through an IV, both processes requiring hospitalization.

In the clinical trials, 29 out of 30 patients given Casgevy and tracked for a minimum of 16 months showed no pain crises for a year.

However, risks are involved in the treatment. Chemotherapy can escalate the risk of blood cancer and infertility, and in the short term, it can eliminate immune cells, potentially increasing a patient's risk of fatal infections.

Morrone acknowledges these risks but suggests for some patients, the promise of a pain-free year may balance them out. She advocates for deliberation in patients' decisions, given not all the potential risks and outcomes may yet be understood.

At the Oct. 31 meeting, advisors to the FDA also discussed the potential for unintended edits, or “off-target effects.” An analysis by Vertex found no evidence of such unwanted changes in treated patients, although researchers have identified a rare variation in the DNA of some people that could, in theory, be an accidental target.  

It’s unknown whether changing that accidental target would have consequences for patients, but researchers say it’s unlikely because that stretch of DNA isn’t involved in a protein’s structure or function. Nor is the protein made from that genetic code found in blood cells. Overall, the 14-member committee agreed that the benefits of the treatment were clear and the off-target risk is small, but that additional research would be helpful. 

Another concern is that the therapy is expensive, perhaps as much as $2 million per patient. But health care costs for sickle cell patients are also high over their lifetime, Morrone says. The health care community needs to consider ways to ensure equity for patients — including in Africa, where the highest burden of disease is — who have long not had the same resources as patients with other conditions with far more treatment options. “There’s not a value on suffering,” she says.  

On November 16, officials in the United Kingdom became the first to sign off on Casgevy’s use in sickle cell patients as well as people with beta-thalassemia, a blood disorder in which the body doesn’t make enough hemoglobin. The FDA will decide by March 30 whether the CRISPR therapy can also be used to treat beta-thalassemia by March 30.

Senior staff writer Tina Hesman Saey contributed to this story.