In a landmark decision, the Food and Drug Administration Friday approved the first gene-editing treatment to alleviate human illness.

The FDA approved two gene therapies for anyone 12 and older suffering from the most severe form of sickle cell disease, a brutal blood disorder that has long been neglected by medical research.

The decisions are being hailed as milestones for treating sickle cell and for the rapidly advancing field of gene editing, which is stirring excitement for treatment of many diseases.

"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 holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited."

"I'm elated, excited, in awe," Jennifer Doudna of the University of California, Berkeley, who helped discover the gene-editing technique called CRISPR that is used in one of the sickle cell treatments, told NPR in an interview. "It's an exciting day and the beginning of a new day in medicine."

For the CRISPR treatment, which was developed by Vertex Pharmaceuticals and CRISPR Therapeutics, both in Boston, doctors remove cells from each patient's bone marrow, edit a gene with CRISPR and then infuse billions of the modified cells back into patients.

The edited cells produce a form of hemoglobin known as fetal hemoglobin, restoring 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.

In data presented to the FDA, the treatment resolved the severe pain crises for at least 18 months for 29 of the subjects — 96.7%. The treatment has produced similar results for patients suffering from a related condition known as beta thalassemia.

The FDA approved another gene therapy called Lyfgenia, developed by bluebird bio inc. of Somerville, Mass., that doesn't use CRISPR to treat sickle cell disease. Instead, Lyfgenia uses a more conventional form of gene therapy that uses a virus to ferry a gene into cells.

Treatment comes with a high price

But the elation over the approvals was tempered by concerns the breakthrough treatments may not be accessible to many sickle cell patients.

They are both very expensive. Vertex said the wholesale price for Casgevy will be $2.2 million. Bluebird set the wholesale price of Lyfgenia at $3.1 million.

The treatments also require a complicated, arduous procedure that many hospitals are not equipped to provide. Many patients may find treatment too physically and logistically daunting.

"We have a lot more work to do" to make gene-editing treatments widely available, Berkeley's Doudna says.

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 excruciating, unpredictable attacks of pain and damages vital organs, cutting patients' lives short.

Sickle cell disproportionately occurs among people of African, Middle Eastern and Indian descent, affecting millions around the world and about 100,000 in the U.S. Although a rare disease, sickle cell is one of the most common genetic disorders.

Some patients can be cured by bone marrow transplants, but most can't find a suitable donor. About 20,000 patients in the U.S. have the severe form of the disease the CRISPR treatment would initially be used to treat.

"I'm really excited," Dr. Lewis Hsu, a pediatric hematologist at the University of Illinois at Chicago who serves as the chief medical officer at the Sickle Cell Association of America, told NPR in an interview. "This is something that we've been waiting for in the sickle cell community for basically 70 years. This is a very big deal."

A life transformed

The approval of the CRISPR gene-editing treatment was also welcomed by Victoria Gray, a Forest, Miss., sickle cell patient who was the first person to receive it in the U.S. NPR has had exclusive access to chronicle her experience since she was treated in 2019.

"I'm ecstatic. It's a blessing that they approved this therapy. It's a new beginning for people with sickle cell disease," Gray told NPR in her latest interview with NPR.

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 was unable to finish school, hold jobs or often even care for herself or her children.

"This has turned my life around. It gave me a new lease on life. It's transformed my life more than I could have ever imagined," Gray says.

Since the treatment, Gray's has been much more energetic and able to start working full time selling cosmetics at Walmart and spend more time with her four children, who are now teenagers.

"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 limitless now. I'm full of energy. I don't have pain. It's a real transformation."

Technical complexity and lengthy hospitalization

Aside from the price for the treatments, another concern is the procedures are long, difficult and complex, requiring multiple trips to a hospital for testing, a grueling and potentially dangerous bone marrow transplant, and lengthy hospitalization. Those factors may put the treatment out of reach for those who need it most in the U.S., as well as in less affluent countries where the disease is most common.

"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."

Many of the countries where most sickle cells patients live don't have enough sophisticated medical centers to provide the complicated treatment. Even in the U.S., the treatment may not be widely available, making it difficult to access.

"Rural patients will likely to be at a disadvantage. And there might be whole states or regions with no gene-therapy options," Hsu says.

More gene-editing treatments are in the works

Doudna heads a center at Berkeley to try to make gene-editing treatments simpler and therefore more accessible. The National Institutes of Health is also trying to address the problem.

The biotech companies say they are working with private and public insurers to cover the procedure. Advocates note that the high price could easily be offset by the savings of avoiding a lifetime of sickle cell complications.

Another concern is whether sufficient research had been done to spot "off-target" effects of the treatment — unintended editing errors that missed their mark in the DNA and that could potentially cause long-term health problems. The FDA is warning Lyfgenia, which uses the more conventional form of gene therapy, may increase the risk for blood cancer.

The companies are planning to follow all the patients treated in the study for 15 years to see how long the benefits last, if the treatment actually helps patients live longer and watch for any signs of long-term complications.

CRISPR based treatments have also shown promise for treated a rare liver condition known as amyloidosis, as well as an inherited form of high cholesterol known as familial hypercholesterolemia.

"It's only the beginning," CRISPR researcher Doudna says.

Copyright 2023 NPR. To see more, visit https://www.npr.org.