FDA approves two gene therapies for sickle cell patients, including one that uses CRISPR tech – giving hope to 100,000 Americans with incurable disease

In a groundbreaking move, the Food and Drug Administration has approved the first gene therapy to treat patients with sickle cell disease, a devastating disease that leaves patients with life-altering pain.

On Friday, the administration gave the green light to Casgevy and Lyfgenia to treat sickle cell disease in patients 12 years and older.

Casgevy is the first FDA-approved treatment to use a new gene-editing technology called CRISPR. To treat this disease, Lyfgenia uses traditional gene therapy rather than gene editing.

Sickle cell disease is a general term for a group of inherited diseases that severely affect the shape and function of red blood cells. It affects 100,000 Americans and 15,000 Britons, the majority of whom are black.

These treatments could offer hope to tens of thousands of Americans with a disease that has been treated only with a bone marrow transplant, an invasive procedure for which most patients are not eligible.

Dr. Reshma Kewalramani, CEO and President of Vertex Pharmaceuticals, one of the companies behind Casgevy, said, “The FDA’s approval of CASGEVY is significant: it is the first CRISPR-based gene editing therapy approved in the United States.”

However, while this news brings hope to patients with sickle cell disease, there are concerns in the medical community that these treatments will be difficult to access due to the expected high cost and limited number of hospitals capable of administering them.

Patients with sickle cell disease, of whom there are about 100,000 in the United States, do not properly produce hemoglobin, the substance in red blood cells that carries oxygen throughout the body. As a result, their red blood cells become stiff and take on a crescent shape (pictured) rather than a disc, which can cause them to die and become stuck in blood vessels.

Casgevy, created by Boston-based Vertex Pharmaceuticals (pictured) and Switzerland-based Crispr Therapeutics, works by editing the defective HBB gene, which underlies both conditions, in a patient’s bone marrow stem cells so that the body produces functioning hemoglobin.

In a healthy person, red blood cells produced by bone marrow stem cells are round, concave discs that bend and flex easily.

However, in people with sickle cell disease, defective stem cells produce sickle-shaped red blood cells. These cells are tough, unable to squeeze through smaller blood vessels and are prone to blockages that deprive parts of the body of oxygen, leading to enormous pain and organ damage.

Until now, bone marrow transplantation was the only approved treatment for this disease. A transplant is a procedure in which healthy blood-forming stem cells are transplanted from a healthy donor to replace a patient’s bone marrow that is not producing enough healthy cells.

Stem cells are the body’s “raw material,” or cells that are capable of developing into many different specialized cell types. They can be used to repair damaged tissue, and researchers believe stem cell therapy could one day treat conditions such as Alzheimer’s disease and paralysis.

In most bone marrow transplant cases, the donor is a sibling, but even a sibling has only a one in four chance of matching the patient. And often transplants are not performed because of the risks, which include the transplanted cells attacking other cells in the recipient’s body, which can be life-threatening.

More than 30 FDA-approved gene therapies are used to treat several different types of cancer and hemophilia, a blood disorder. However, many of them are largely inaccessible due to high costs.

Kasjevy was recently approved in the UK to treat sickle cell and transfusion-dependent β-thalassemia, a red blood cell deficiency that leads to severe anemia. It is expected to cost the UK government around $1.25 million (£1 million) per patient.

Created by Boston-based Vertex Pharmaceuticals and Switzerland-based Crispr Therapeutics, Casgevy is the first licensed drug to use the innovative gene-editing tool CRISPR. This process is known as “genetic scissors” and allows scientists to make precise changes to DNA. Its inventors were awarded the Nobel Prize in 2020.

The therapy works by editing the faulty HBB gene that causes sickle cell disease in a patient’s bone marrow stem cells so the body can produce properly functioning hemoglobin, the protein in red blood cells responsible for delivering oxygen to tissues throughout the body.

To do this, stem cells are extracted from the patient’s bone marrow and edited in the laboratory using molecular scissors that precisely turn off the faulty gene.

The stem cells are then infused back into the patient, who may have to spend a month or longer in the hospital until the treated cells begin producing healthy red blood cells.

Scientists believe the results may last a lifetime.

Ongoing trials of the drug so far show that 97 percent of patients with sickle cell disease did not experience severe pain for at least one year after treatment.

Dr. Kewalramani added: “Equally important, Kasjevy is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease.

“I want to express my deepest gratitude to the patients and researchers whose trust in this program paved the way for this landmark approval.”