- For the first time, the FDA has approved gene therapies to treat sickle cell disease.
- The treatments change the type of red blood cells made by the body, which eliminates complications of sickle cell disease, such as infections and stroke.
- One treatment uses the CRISPR-Cas9 gene-editing system. The other uses a different method to insert a gene into stem cells.
Two new genetic therapies that can potentially cure sickle cell disease have been approved by the U.S. Food and Drug Administration (FDA).
“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” said Dr. Nicole Verdun, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research in a
“Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited,” she said.
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 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).
One of the treatments is called Casgevy. It is a cell-based gene therapy made by Vertex Pharmaceuticals and CRISPR Therapeutics. This is the first approved therapy based on CRISPR.
It involves editing the genes in bone marrow stem cells.
This changes the type of red blood cells made in the body, allowing cells to go back to producing fetal hemoglobin. 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, said in an earlier interview that this treatment could be a milestone for gene-editing.
“This will be the first [CRISPR] gene-editing-based treatment of sickle cell disease — or any disease — for use in the clinic,” he told Healthline in an earlier interview. Bao has not worked on the treatment.
The second therapy is called Lyfgenia made by blubird bio, inc. This uses a genetic delivery vehicle called a vector to cause genetic modification. The patients’ blood stem cells are modified to produce a type of hemoglobin that is closer to hemoglobin A. That is the normal hemoglobin found in people without sickle cell disease.
Some patients treated with Lyfgenia developed blood cancer, so a black box warning has been added to the treatment’s label, the
Both therapies are approved for people aged 12 and over.
Dr. Zahra Pakbaz, a hematologist with UCI Health, said there is an urgent need for new treatments like these for sickle cell disease.
“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
This disease affects more than 100,000 people in the United States and 20 million people worldwide, according to the
It is more common among people who are Black or of African ancestry. In the United States, about
Previous to these drugs, 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
While the new treatment options are a major breakthrough for patients, cost could remain a barrier.
The treatments are 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.
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 in an earlier interview. “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.
Dr. Joseph Wu, a professor of medicine and radiology at Stanford University, agreed, saying in an earlier interview, “These patients are quite sick and this is a very good therapy.”
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.
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.”
“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.”
For the first time, FDA has approved two new gene therapies to treat sickle cell disease.
Both involve modifying red blood cells so they don’t “sickle” or become crescent-shaped.
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.