Casgevy: A Cell-Based Gene Therapy for a Rare Blood Disorder and Its Possible Use to Reduce Severe Pain Crises

“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 statement. Gene therapy has promise of delivering more targeted and effective treatments for individuals with rare diseases who face limited treatment options.

The treatment for the CRISPR drug uses removing cells from each patient’s bone marrow, editing a gene with the drug, and then returning billions of the modified cells to patients.

Fetal hemoglobin is a form of red blood cell hemoglobin and it restores normal function of red blood cells. While not a cure for the disease, the hope is the therapy, brand name Casgevy, is designed to be a one-time treatment that will alleviate symptoms for a lifetime.

The treatment solved severe pain crises for at least 18 months in 29 of the subjects, a rate of 96.7%. The treatment has produced similar results for patients suffering from a related condition known as beta thalassemia.

CRISPR versus Blood Transfusion for Sickle Cell Disease: A Case Study of Mary Gray and her Loss of Working and Getting Away

They are both very expensive. The wholesale price will be over $2 million. The price was set at more than three million dollars.

The procedures are lengthy, difficult and complex, requiring multiple trips to a hospital for testing, and a potentially dangerous bone marrow transplant, both of which can cause long hospitalizations. Those factors may make treatment out of reach for people in the U.S. who are most in need and for people in less affluent countries.

Gene-editing, which allows scientists to manipulate the basic building blocks of life more easily than ever before, is being studied as a treatment for illnesses ranging from rare genetic disorders like muscular dystrophy to common ailments like cancer, heart disease, diabetes, AIDS and Alzheimer’s.

Sickle cell disease is caused by a genetic defect that produces an abnormal form of the protein hemoglobin, which red blood cells need to carry oxygen through the body. As a result, the red blood cells of sickle cell patients become misshapen sickle-shaped cells that get jammed inside blood vessels. That causes a series of attacks of pain and damages vital organs, which causes patients’ lives to be shortened.

Like many sickle cell patients, Gray was forced throughout her life to repeatedly rush to the hospital for powerful pain drugs and blood transfusions. She could not go to school, work, or care for herself or her children.

Gray’s was able to work full time at Walmart, and spend more time with her children, as a result of the treatment.

“Since I received the CRISPR treatment, I’ve had a new beginning. Most of all, I no longer have to fear dying and leaving my kids behind without a mother,” Gray says. My life is not limited anymore. I’m awake and full of energy. I have no pain. It’s a real change.

“I have a mixed reaction,” says Melissa Creary, an assistant professor at the University of Michigan who studies sickle cell at the University of Michigan School of Public Health and has the disease herself. “I am excited about the promise that this technology has for those living with sickle cell disease. But as this technology comes to market it’s going to be really interesting to see the ways in which profit overtake social justice.”

Most of the countries where most of the people with sickle cells live doesn’t have enough state-of-the-art medical centers to provide complicated treatment. Even in the U.S., the treatment may not be widely available, making it difficult to access.

A CRISPR based approach to improving the lives of a rare liver condition and an inherited form of high cholesterol in the early stage of cancer

Unintended edits that missed their mark in the genome could cause long-term health problems, and there’s a concern about whether sufficient research had been done to spot off-target effects.

If the treatment can help patients live longer, they will be followed by the companies for 15 years to see how long the benefits last.

Potential treatments for a rare liver condition known as amyloidosis and an inherited form of high cholesterol have been shown to be provided with CRISPR based treatments.

“This is a major milestone,” says Vence Bonham, acting deputy director of the National Human Genome Research Institute at the National Institutes of Health. It could change the lives of individuals and help decrease the burden of pain episodes.