A New Treatment for Sickle Cell Anemia May Soon Be Available, What to Know

A man in green shirt talks to physician in white shirt and black pants.
There may soon be a a new treatment for sickle cell anemia that uses gene-editing techniques. SDI Productions/Getty Images
  • An FDA advisory committee reviewed the safety of a treatment for sickle cell disease that uses the CRISPR-Cas9 gene-editing system.
  • The treatment changes the type of red blood cells made by the body, which eliminates complications of sickle cell disease, such as infections and stroke.
  • Committee members said the benefits of the treatment outweigh the risks. The FDA still has to make a final decision on the treatment.

A new genetic therapy that can potentially cure sickle cell disease may soon be approved by the U.S. Food and Drug Administration (FDA), after an independent agency advisory committee said it was safe for clinical use.

The treatment, called exa-cel and jointly developed by Vertex Pharmaceuticals of Boston and CRISPR Therapeutics of Switzerland, involves editing the genes in bone marrow stem cells. 

This changes the type of red blood cells made in the body. After treatment, red blood cells no longer form the “sickle” or crescent shape that causes problems in people with sickle cell disease.

Gang Bao, PhD, a professor of bioengineering and of chemistry and materials science and nano-engineering at Rice University, called this a milestone for gene-editing.

“If approved, this will be the first gene-editing-based treatment of sickle cell disease — or any disease — for use in the clinic,” he told Healthline. Bao has not worked on the treatment.

While this treatment for sickle cell disease has advanced furthest in clinical trials, “I believe that there will be a lot more clinical trials on treatments for other diseases using CRISPR,” he added.

What is sickle cell disease?

Sickle cell disease is a group of inherited conditions that affect hemoglobin, a protein found in red blood cells that carries oxygen throughout the body.

Normally, red blood cells are disc-shaped and flexible enough to easily move through blood vessels. In sickle cell disease, a genetic mutation causes the cells to become “sickle”— or crescent-shaped. 

Sickled red blood blood cells cannot bend easily, which makes it hard for them to move through blood vessels. This can block the blood flow to parts of the body and cause serious problems, including stroke, infections, eye problems, and episodes of pain (known as pain crises).

Dr. Zahra Pakbaz, a hematologist with UCI Health, said there is an urgent need for new treatments like the reviewed by the FDA committee.

“This is a devastating disease,” she told Healthline. “Pain crises are unexpected and recurrent, and in many cases, pain is chronic and does not go away.”

In addition, “this is a progressive disease,” she said. “The organ damage [that occurs] is not reversible, and it gets worse over time.”

The complications associated with sickle cell disease can lead to an early death.

“There is plenty of data showing sickle cell disease has impaired the quality of life and life expectancy of individuals with this condition, regardless of which country they live in,” said Pakbaz.

In 2017, Americans with sickle cell disease had an average life span of 43 years, according to the Centers for Disease Control and Prevention, an increase from 28 years in 1979.

This disease affects more than 100,000 people in the United States and 20 million people worldwide, according to the National Institutes of Health.

It is more common among people who are Black or of African ancestry. In the United States, about 1 in 365 babies who are Black are born with sickle cell disease. However, Pakbaz said others can also be affected by this disease, including Hispanics and white people.

Currently, the only cure for sickle cell disease is a bone marrow transplant. However, this requires finding a matched donor, which Pakbaz said aren’t available for many patients. After the surgery, people have to regularly take drugs to prevent the body from rejecting the transplanted cells.

Medicines and taking other steps can help people manage their condition at home.

How does the treatment work?

The treatment developed by Vertex and CRISPR Therapeutics uses the CRISPR-Cas9 gene-editing system, which can cut a cell’s DNA at a targeted location. This can be used to turn genes on or off.

To treat sick cell disease, CRISPR is used to cut DNA in bone marrow stem cells at a specific location. This activates a blocked gene that produces a form of hemoglobin usually only found in a fetus. The fetal hemoglobin does not form the sickle shape.

While this treatment can cure sickle cell disease, it is intensive, according to a summary from the Sickle Cell Disease Association of America. Patients first undergo a treatment to cause bone marrow stem cells to enter the bloodstream. These cells are collected from the blood, and then modified with CRISPR and grown in a lab.

Before the modified stem cells can be infused into a patient, the person has to undergo intense chemotherapy to remove the original stem cells from the bone marrow. After infusion, patients stay in the hospital while the new cells grow in the bone marrow.

If approved, the treatment would be available to people 12 years and older.

The treatment is expected to cost millions of dollars per patient, according to the Sickle Cell Disease Association of America. However, it may be worth it. Current care for patients with the disease costs an estimated $3 billion a year.

Advisory group highlights safety

During a 7-hour meeting on Oct. 31, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee discussed potential safety issues with the genetic treatment.

One of these involves where the DNA editing occurs.

“You design the CRISPR system to cut at a particular location of the genome,” said Bao, who is not a member of the advisory committee. “But the system can cut at other locations in the genome, what’s called off-target editing.”

Off-target editing can potentially disrupt or activate another gene, which can lead to a harmful outcome such as a blood cancer.

Bao said problems can also occur even if the editing occurs at the right location.

“There could be large deletions, large insertions or complex changes of the genome at the on-target site,” he said, something he and his colleagues discussed in a recent paper published in the Current Opinion in Biomedical Engineering.

The clinical trial that tested exa-cel did not identify any issues with off-target editing, reports The New York Times. However, the trial included just 44 patients, with only 30 followed for at least 16 months. 

The FDA recommends following patients for 15 years after treatment.

Another potential problem with the treatment is that the chemotherapy used to eliminate stem cells from the bone marrow can increase the risk of complications such as infertility or cancer, said the Sickle Cell Disease Association of America.

At the FDA meeting, the companies shared details of the work they did to make sure off-target editing wasn’t happening. But Bao thinks they should have done more to ensure the treatment is safe.

Similar concerns were raised by the FDA’s advisory committee during the meeting. But after reviewing clinical trial data, members felt that the treatment was safe enough to move forward.

“I think the benefits far outweigh the risks,” said committee member Alexis Komor, PhD, an assistant professor of chemistry and biochemistry at the University of California, San Diego.

Dr. Joseph Wu, a professor of medicine and radiology at Stanford University, agreed, adding, “These patients are quite sick and this is a very good therapy.”

Scot Wolfe, PhD, a professor of molecular, cell and cancer biology at the University of Massachusetts Chan Medical School, cautioned against waiting too long to offer this treatment to patients.

“There’s a huge unmet need for individuals with sickle cell disease,” he said. “It’s important that we think about how we can advance therapies that could potentially help them.”

“And I certainly think that this [treatment] is one of them,” he added.

While it remains to be seen how many patients will sign up for this new treatment if it is approved, Pakbaz thinks many will consider it.

“If you talk to patients and families, they are very supportive of the idea of finding a cure, and of clinical trials to find a cure,” she said, “especially given the short, painful life expectancy they face.”

One recent study, published in Blood Advances, found that people with more severe sickle cell disease had a higher tolerance for the risks associated with gene therapies.

“The key is to be open with families about the limitations and risks [of the treatment],” said Pakbaz, “and to individualize patients’ plan of care.”

Takeaway

If approved by the FDA, a new treatment for sickle cell disease that uses the CRISPR-Cas9 gene-editing system would offer people with this condition another option.

The treatment involves collecting bone marrow stem cells, editing the DNA, and infusing those cells back into a patient. The body would then produce normal red blood cells, which would eliminate the complications of sickle cell disease.

The treatment could cost millions of dollars per patient, but the cost to the U.S. healthcare system of this disease is currently billions of dollars per year.

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