FDA Approves the First Gene-Editing Treatment for Sickle Cell Disease

Fact checked by Nick Blackmer

Key Takeaways

• The FDA approved a groundbreaking treatment to cure sickle cell disease by using CRISPR gene-editing technology.

• An FDA panel said the treatment is safe enough for clinical use.

• Before the approval, the only cure for the disease was a bone marrow transplant.
  

The Food and Drug Administration (FDA) has approved the first-ever genetic therapy that can potentially cure sickle cell disease, which causes excruciating pain in patients.

An FDA advisory panel said that the treatment, which uses the groundbreaking gene-editing technique called CRISPR, is safe for clinical use.

The treatment, called Casgevy, is developed by Vertex Pharmaceuticals and CRISPR Therapeutics. Before this approval, the only other cure for the disease was a bone marrow transplant from a donor, a treatment that very few people choose to undergo because of the risks.

Sickle cell disease is a group of inherited red blood cell disorders in which the red blood cells become hard and sticky, resembling a C-shaped farm tool called a “sickle,” according to the Centers for Disease Control and Prevention (CDC). It affects approximately 100,000 people in the United States, the majority of whom are Black.

People with sickle cell disease have abnormal hemoglobin and their sickle cells die earlier, leading to a shortage of red blood cells. The first signs of the disease usually show up within the first year of life. The symptoms are different for everyone and can range from mild to severe, but some of the most common complications include anemia, blood clots, liver problems, organ damage, pain, and stroke.

There’s no question that the new gene therapy can cure the disease, according to Jeffrey Glassberg, MD, an assistant professor of emergency medicine, hematology, and medical oncology at Mount Sinai School of Medicine.

“This is a cure. The issue is that it comes with risks that most people will not want to take,” Glassberg told Verywell.

Related: What Is Sickle Cell Crisis?

How Does the Treatment Work?

Researchers can use CRISPR to cut DNA in specific places to add, delete, or replace sequences, unlocking the potential to treat a whole category of diseases that were previously deemed “undruggable,” Glassberg explained.

The treatment works by extracting stem cells from the patient’s blood and editing them in a lab to cut out the part of the DNA that is causing misshaped cells. The patient must then undergo chemotherapy before the edited stem cells can be inserted back into the patient.

“CRISPR proteins and their guides are not perfect,” Glassberg said. “Sometimes the guides can match up with DNA in unintended locations, causing unwanted cuts. Most of the time, these ‘off-target’ hits are harmless, but very rarely they can be dangerous.”

Much of the danger depends on how many places in the DNA are a close but not-perfect match for the guide, and what functions those locations have, he said. In the case of CRISPR therapeutics, the potential for dangerous off-target hits was deemed extraordinarily low, but the FDA did point out that Vertex did not use enough DNA from people with sickle cell disease (i.e., they used genomes from other populations) to predict what off-target hits were likely to occur.

“Based on my understanding, you are more likely to get hit by lightning on the way to the hospital than you are to have a catastrophic off-target edit from the CRISPR,” he said.

The more concerning safety issues, however, lie in the other medicines that need to be taken to make the therapy work, he said. This includes busulfan, which is needed to clear out the bone marrow to make room for the gene-edited stem cells. Busulfan is known to raise the risk of cancer, and all existing sickle cell gene therapies (CRISPR and non-CRISPR) use busulfan.

There is approximately a 1% risk of death with the treatment, and it often causes infertility, he said.

This treatment requires a bone marrow transplant unit, with which not all hospitals are equipped, raising the issue of access, Glassberg said. And while Vertex has not yet disclosed the price of the treatment, there are estimates that it could cost as much as $2 million per patient.

“Someday we hope to develop a gene therapy that does not require chemotherapy or bone marrow transplant units,” Glassberg said. “Instead of taking stem cells out and editing them in a lab, we would inject the CRISPR into the patient like a drug. This could be a cure that would not cause infertility or death, and could be accessed worldwide.”

What This Means For You

There's now an FDA-approved gene therapy for sickle cell disease. An FDA panel said the treatment is safe enough for clinical use. However, this treatment might come with a hefty price tag.

Read the original article on Verywell Health.