Gene-Editing Treatment for Sickle Cell Disease Moves Closer to Approval

FDA advisors said the benefits seem to outweigh any possible risks, and the agency will decide whether to approve it by December 8

A zoomed in view of both normal, round red blood cells, and crescent-shaped sickle cells
A blood smear of a patient with sickle cell. The crescent-shaped sickle cells can be seen in the smear. Cultura RM Exclusive / Michael J. Klein, M.D.

An experimental new gene-editing treatment for sickle cell disease has inched a step closer to approval, following a discussion among Food and Drug Administration (FDA) advisors on Tuesday.

The committee did not vote on the efficacy or safety of the potential cure, but many of the panelists expressed that its benefits seem to outweigh the possible risks, writes MedPage Today’s Mike Bassett.

Now, the FDA must rule on the treatment by December 8, and following this week’s meeting, the agency appears likely to approve it, according to the New York Times’ Gina Kolata.

The treatment involves CRISPR, a gene-editing technology that can tweak DNA at precise locations. If given the green light, it would become the first FDA-approved treatment to employ CRISPR.

“We are finally at a spot where we can envision broadly available cures for sickle cell disease,” said John Tisdale, a member of the advisory committee who researches sickle cell disease at the National Heart, Lung and Blood Institute, per the New York Times.

Sickle cell disease refers to a group of inherited blood cell disorders that affect hemoglobin, a protein that carries oxygen. In people with the condition, an abnormal form of hemoglobin causes red blood cells to become crescent-shaped instead of round. These misshapen cells can get stuck in blood vessels and clog blood flow, leading to pain, infection, strokes or other health problems. People with sickle cell disease live 42 to 47 years on average.

More than 100,000 people in the U.S. and 20 million people worldwide have sickle cell disease. Currently, the only cure is a bone marrow transplant, though other treatments can reduce symptoms and increase life expectancy. Most Americans with the condition are of African ancestry or identify as Black, and it also affects many people from Hispanic, Southern European, Middle Eastern or South Asian backgrounds.

The new treatment, called exa-cel, edits cells with CRISPR so that they produce a form of hemoglobin that restores normal red blood cell function, writes NPR’s Rob Stein. The treatment requires removing cells from the patient’s bone marrow, editing a gene and infusing the cells back into the patient.

In an ongoing study, 29 of 30 patients who received the treatment did not experience any severe pain crises for 12 months afterward. On average, the patients had more than four such crises per year prior to treatment.

The FDA asked its advisors to discuss how it should consider the possibility of “off target” edits, or the chance that the technology would accidentally change other parts of DNA, per NBC News’ Berkeley Lovelace Jr. and Marina Kopf. While this did not occur in the clinical trial, only a small group was measured—just 30 of the 44 total participants were followed for at least 16 months, per the New York Times. But some panelists felt the benefits were apparent enough to let the treatment move forward.

“There seems to be a strong sense of benefit, and the risk is theoretical,” said Tabassum Ahsan, the committee chair and vice president of cell therapy operations at City of Hope, per MedPage Today.

“It’s really exciting to see how many patients have been treated and how positive the results have been,” said Scot Wolfe, a member of the advisory committee who researches gene editing technologies at the UMass Chan Medical School, per NPR. “We want to be careful to not let the perfect be the enemy of the good.”

Others said that more research could be beneficial.

“I’m not questioning that this product is important for our patients,” said Joseph Wu, a committee member and cardiologist at Stanford University, per NBC News. “I’m just saying we’re at a point in which this thing is going to take off, and wouldn’t it be nice to have more additional data.”

Notably, the gene therapy has monetary and other costs. The arduous treatment involves blood transfusions, chemotherapy and a long hospital stay. And it may also cost as much as $2 million per patient.

Vertex Pharmaceuticals, one of the treatment’s developers, says Medicaid and private insurers have suggested they are willing to pay for it, per the New York Times. Young children with the condition, as well as older patients for whom the disease has caused a lot of damage, may not be eligible for the treatment.

“I’m worried that this will be a very highly lauded technology that people will not be able to use,” Melissa Creary, who studies sickle cell at the University of Michigan, tells NPR. “I think the people who need this therapy the most will not be able to afford it.”

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