Until recently, the only possible cure for sickle cell disease, an inherited genetic blood disorder most common in people with African ancestry, was a bone marrow transplant, which has its own set of challenges.

Now, people with sickle cell disease (SCD)which affects an estimated 100,000 Americans and can cause chronic pain, organ damage, strokes, and shortened life expectancyhave additional, potentially curative options. In early December, the Food and Drug Administration (FDA) approved two gene therapies for SCD, one of which is the first approved medication that uses the gene-editing tool CRISPR.

Both treatmentsCasgevy, which is made by Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia, by Bluebird Bioare for people 12 and older. Sickle cell disease is a red blood cell disorder that affects hemoglobin, the protein that carries oxygen throughout the body. These two therapies work in different ways, but both are intended to be a one-time fix, although that will require years of follow-up to know for sure.

With Casgevy, an edit (or cut) is made in a particular gene to reactivate the production of fetal hemoglobin, which dilutes the faulty red blood cells caused by sickle cell disease (more on that below). Lyfgenia, on the other hand, uses a viral envelope to deliver a healthy hemoglobin-producing gene.

The therapies are hailed as groundbreaking as they represent the first-ever gene therapies to potentially cure a hereditary condition.

For many years, we only had one treatment for sickle cell disease, and then medicine advanced to the point where we could offer bone marrow transplant, the first potential cure for sickle cell disease, says Cece Calhoun, MD, MBA, a Yale Medicine hematologist-oncologist. But trying to find a good match for a transplant is a big barrier. This new technology uses gene therapy to allow patients to be their own match.

This is significant, she notes, because a sickle cell crisisthe pain the disease causesis unpredictable and intense, akin to how it feels to have a long bone fracture.

But, says Dr. Calhoun, the pain sickle cell disease causes is not the only problem faced by people with the condition.

Sickle cell disease impacts every organ. Children are having strokes, and young adultspeople in their 30sare experiencing kidney failureall because of sickle cell disease. If we can intervene and prevent these complications and let these patients live full lives, that is huge, Dr. Calhoun says.

Lakshmanan Krishnamurti, MD, chief of Yale Medicine Pediatric Hematology & Oncology, agrees.

Many cant have bone marrow transplantation because only about 15% of patients have a matched sibling, and we can find an unrelated donor for only another 10% to 12%. That means we are only helping 25% of patients, says Dr. Krishnamurti, who was an author on the Lyfgenia study published in The New England Journal of Medicine. This is a big step forward.

However, the gene therapies are time-intensivetaking about a year to complete the processand grueling. As with bone marrow transplants, they require high-dose chemotherapy to kill the faulty stem cells before they are replaced with modified stem cells.

The gene therapies will be available only at large, authorized medical centers because they require advanced care. They are also expensive (estimates put it at $2 to $3 million per patient), and its yet to be determined if or how insurance companies, including Medicaid, will cover the treatment.

Dr. Krishnamurti says both treatments will be available at Yale and that anyone interested in learning more should speak to their physician.

Below, Drs. Calhoun and Krishnamurti answer common questions about sickle cell disease and these new gene therapies.

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Casgevy and Lyfgenia: Two Gene Therapies Approved for Sickle Cell Disease - Yale Medicine