What to Know About 2 New Gene Therapies for Sickle Cell Disease

Sickle cell disease, a painful inherited blood disorder that predominantly impacts Black people, can now be treated with gene therapies that dramatically reduce symptoms and have the potential to one day offer a cure.

The U.S. Food and Drug Administration (FDA) approved two gene therapies for sickle cell disease, Casgevy and Lyfgenia, on December 8. Both treatments work by genetically modifying patients’ own stem cells and are cleared for use by people age 12 and older, the FDA said in a statement.

“This is a monumental moment,” says Markus Mapara, MD, PhD, a professor and the director of the blood and marrow transplantation program at Columbia University Irving Medical Center in New York City.

“It is too early to determine whether the new gene therapies will lead to sustained and long-term reversal of the symptoms of sickle cell disease,” says Dr. Mapara, who has worked as a consultant for companies involved in both treatments. “But the current results look very promising.”

Sickle cell disease is a group of rare disorders that impact about 100,000 people in the United States, most of whom are Black, according to the FDA. It’s caused by a mutation in hemoglobin, a protein in red blood cells that carries oxygen around the body. Red blood cells with this mutation have a sickle shape that clogs blood vessels and limits how much oxygen reaches tissues and organs. This can cause debilitating pain, frequent hospitalizations, and premature death.

New Infusions for Sickle Cell Disease Are Made From Patients’ Own Cells

There are several medications that can treat health problems associated with sickle cell disease, including anemia, infections, stroke, and kidney damage, Mapara says. Until now, however, the only cure has been a bone marrow transplant. This is a complex process that requires chemotherapy to kill abnormal bone marrow responsible for making defective, sickle-cell-shaped hemoglobin, followed by a transplant of healthy cells donated from a sibling.

Rather than using a donor, the new treatments create a unique infusion using a person’s existing stem cells. Before they receive the infusions, though, patients still must undergo high-dose chemotherapy.

Casgevy is the first drug approved in the United States that uses the gene-editing tool CRISPR, according to the FDA. It works by editing the DNA in a patient's own stem cells to remove a gene that causes sickle-shaped red blood cells.

Lyfgenia works differently. It uses a deactivated virus to deliver a copy of a gene into patients’ own cells that lets them start making healthy hemoglobin.

Clinical Trials Yielded Positive Results for Casgevy and Lyfgenia

In a clinical trial for Casgevy, 29 of 31 patients with sickle cell disease were free of what’s known as vascular occlusive events — or health problems related to blocked blood vessels — for at least a year after receiving the infusion, according to the FDA. The most common side effects were low levels of blood platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, fever from low white blood cell count, headache, and itching.

In a clinical trial of Lyfgenia, 28 patients with sickle cell disease experienced a complete resolution of vascular occlusive events between 6 and 18 months after receiving the infusion, according to the FDA. The most common side effects included mouth sores and low levels of platelets, white blood cells, and red blood cells, as well as fevers associated with low white blood cell counts.

Lyfgenia also carries a black box warning, reserved for the most severe side effects identified by the FDA, because of its potential to cause blood cancers, the FDA said. Patients who receive this gene therapy will need lifelong monitoring for blood malignancies.

The chemotherapy regimen required before both gene therapies can also cause infertility.

Questions Remain About Cost and Access

Treatment won’t be cheap. Vertex Pharmaceuticals and its partner CRISPR Therapeutics jointly developed Casgevy and said it will cost $2.2 million, according to Reuters. Bluebird Bio, the developer of Lyfgenia, set a $3.1 million price tag for its drug, Reuters reported.

“We don’t know how much the out-of-pocket expenses will be,” Mapara says. “But the costs may be a barrier to access.”

It also won’t be available everywhere. Just nine treatment centers across the country are currently authorized to administer Casgevy, Vertex said in a statement. Bluebird Bio said 27 treatment centers are now able to administer Lyfgenia. Both companies said they anticipate more locations becoming available over time.

Boston Medical Center is one of the treatment centers authorized to administer both Casgevy and Lyfgenia, and the only location in New England. Even though access may initially be limited because of costs and other factors, Jean-Antoine Ribeil, MD, PhD, the clinical director of the Center of Excellence in Sickle Cell Disease at Boston Medical Center, says the FDA approval of these new gene therapies is “monumental.”

“The new therapies leverage the latest advances in medical science to alleviate the devastating pain and long-term health impacts of sickle cell disease, bringing a long-awaited step toward equity in treatment to a disproportionally impacted Black patient population,” Dr. Ribeil says.