By Berkeley Lovelace Jr. and Marina Kopf – NBC News
The Food and Drug Administration on Friday approved a powerful treatment for sickle cell anemia, a devastating disease that affects more than 100,000 Americans, most of them black.
The Casgevy treatment, from drugmakers Vertex Pharmaceuticals and CRISPR Therapeutics, is the first approved in the United States using the gene-editing tool CRISPR, which earned its inventors the Nobel Prize in Chemistry in 2020.
"I think this is a pivotal moment in the field," said Dr. Alexis Thompson, chief of the division of hematology at Children's Hospital of Philadelphia, who has previously been a consultant to Vertex. "It's been really extraordinary how quickly we've gone from CRISPR discovery, to being awarded a Nobel Prize, to getting a product approved."
The approval marks the first of two potential breakthroughs in the treatment of this inherited blood disorder. On Friday, the FDA also gave the go-ahead to a second treatment for sickle cell anemia, called Lyfgenia, a gene therapy from drugmaker Bluebird Bio. Both genetically modify the patient's stem cells.
Until now, the only known cure for sickle cell disease was a bone marrow transplant from a donor, which carries the risk of rejection by the immune system, in addition to the difficult process of finding a match.
Casgevy, approved for people 12 and older, eliminates the need for a donor. Using CRISPR, it edits the DNA of the patient's stem cells to remove the gene that causes the disease.
"The patient is his or her own donor," Thompson says.
"It's a game changer," says Asmaa Ferdjallah, M.D., a pediatric hematologist and bone marrow transplant physician at the Mayo Clinic in Rochester, Minn. "Truly reimagining and rediscussing sickle cell anemia as a curable disease and not as this painful and debilitating chronic disease is hope enough with this news."
Still, the new therapy is expected to be extremely expensive — potentially about $2 million per patient, according to a report by the Institute for Clinical and Economic Review, a nonprofit group that helps determine fair drug prices. According to experts, these costs can put it out of reach for many families. What's more, that price doesn't include the amount of care associated with treatment, such as hospital stay or chemotherapy.
"We really need to make sure it's accessible," says Dr. Rabi Hanna, a pediatric hematologist-oncologist at the Cleveland Clinic who has served on Vertex's advisory board. "This could be a counterbalance for people with sickle cell disease, because many patients can't pursue career options" because of the disease.
"It's something that the families have been aware of in the initial phase of the investigation, and they've been patiently waiting for years," Ferdjallah said. "It's been eagerly awaited by patients and families, but also by providers and doctors."
How Casgevy works
In patients with sickle cell anemia, the red blood cells, which are usually disc-shaped, take on a crescent or sickle shape. This change can cause cells to clump together, leading to clots and blockages in blood vessels, depriving tissues of oxygen. Patients can suffer excruciating pain, breathing problems, and strokes.
Casgevy works by editing the DNA of the patient's stem cells, which are responsible for making blood cells, so that they stop producing sickle cells.
Although it is technically a one-time treatment, before the patient receives the modified stem cells, a series of steps that take months must be followed. It starts with a series of blood transfusions over three to four months, after which stem cells are removed from the patient's bone marrow and sent to a lab where they are edited, Hanna explains.
However, before reinfusing them into the patient, doctors must ensure that no defective stem cells remain in the body. To do this, chemotherapy is used to destroy the patient's bone marrow.
Only then can the edited stem cells be reinfused into the patient, after which they must remain in the hospital for an additional month or two for the cells to grow and the patient to recover.
Hanna says she's always "cautious" when talking to family members and patients about the one-size-fits-all treatment, because they may have unrealistic expectations.
"There are multiple phases to this journey," he said.
The clinical trial involved 46 people from the U.S. and abroad, 30 of whom received at least 18 months of follow-up after treatment. Of those, treatment has been successful in 29.
LaRae Morning, 29, of Phoenix, was one of the patients whose treatment was successful.
Her mother lost several jobs when Morning was a child and teenager due to her frequent visits to the hospital.
In April 2021, Morning joined the clinical trial of HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Children's Hospital in Nashville, Tennessee, a decision she initially regretted. Since I lived in Phoenix, I had to fly to Nashville once a month for treatment. It included several blood transfusions, each lasting eight hours, and taking a drug called plerixafor, which she remembers causing intense stomach pains. When she started chemotherapy, her hair began to fall out and her skin changed color, looking like a chemical burn. She also experienced nausea.
It took him about six to seven months to get back to normal after the CRISPR treatment. Now, he says, he's feeling the benefits, going out to coffee shops, spending time with friends and finishing his first semester of law school in Washington, D.C.
"Now that I'm here, I'm so glad I did it," she says of the trial. "I'm like a normal person. I got up and ran. I lift weights. If I want to swim, I can swim. I'm still trying to figure out how far I can go, what things I can do."
That's been the experience of several other patients in the trial, too, according to Dr. Monica Bhatia, chief of pediatric stem cell transplantation at NewYork-Presbyterian/Columbia University Irving Medical Center. Bhatia is a principal investigator at one of the clinical trial sites in New York.
After treatment, most patients went back to school, went to the gym or resumed other activities — "things that a lot of people take for granted," he said — after about three or four months.
"They can really live without restrictions," Bhatia says.
Dr. Haydar Frangoul, medical director of pediatric hematology-oncology at the Sarah Cannon Research Institute, said he hopes the therapy will bring relief to more patients.
"I think this is a great time for sickle cell patients," said Frangoul, who was the principal investigator of the clinical trial and treated Morning.
Although Casgevy has proven its effectiveness, experts still don't know the potential long-term effects, as the trial will only last two years.
At a meeting in October, an FDA advisory committee discussed the risk of "off-target" effects, meaning when the gene-editing tool makes cuts in stretches of DNA other than the intended target, and how the agency should account for these risks in the future.
It's unclear what effects off-target editing would have on a patient, but it's feared it could have unintended health consequences in the future, according to Thompson. "To date, there don't appear to be any measurable consequences."