A panel of experts said Tuesday that a breakthrough treatment for sickle cell disease is safe enough for clinical use, paving the way for likely federal approval by Dec. 8 of a powerful potential cure for a disease that afflicts more of 100,000 Americans.

The Food and Drug Administration previously found the treatment, known as exa-cel and jointly developed by Vertex Pharmaceuticals of Boston and CRISPR Therapeutics of Switzerland, to be effective. The panel’s conclusion Tuesday on the safety of exa-cel sends it to the FDA for a decision on whether to authorize it for widespread use by patients.

Exa-cel frees patients from the debilitating and painful effects of this chronic and deadly disease. If approved, the Vertex product would be the first drug to treat a genetic disease with the CRISPR gene editing technique.

It could also be the first in a series of new options to cure this terrible disease. By Dec. 20, the FDA will decide on a second potential cure for sickle cell disease, a gene therapy designed by the Somerville, Massachusetts, company Bluebird Bio.

Sickle cell disease is caused by a genetic mutation that distorts blood cells so that they look like sickles or crescents. It affects millions of people around the world, most of whom have African ancestry. The deformed cells get stuck in blood vessels, causing strokes, organ damage and episodes of excruciating pain when muscles lack oxygen.

The consequences of sickle cell disease begin early in life. Evelyn Islam of Milwaukee, now 8, received 22 blood transfusions and had to have her spleen removed before she was 3. “Gene therapy is our last hope for a cure,” said his mother, Melissa Nicole Allen.

But for many, new gene therapies will come too late.

Ashley Valentine, co-founder of the national advocacy group Sick Cells, had to take three months off work in 2016 to help her brother Marqus deal with the symptoms of sickle cell disease. When he had a hip replacement in 2018, his father eventually agreed to be laid off to care for him.

“And it’s just us,” she said.

Marqus died in 2020, at age 36, following a stroke caused by a diseased cell.

New treatments like the one approved Tuesday are expected to cost millions of dollars per patient, although Vertex has not yet said how much it would charge. But lifelong care for patients with the disease is also extremely expensive, costing the healthcare system approximately 3 billion dollars per year.

We do not yet know how many people will use this new therapy. The new therapies are also not easy to tolerate and cause difficulties for patients, who will have to undergo chemotherapy and spend more than a month in hospital. Family members are also affected: they may have to take time off work during the most intensive phase of treatment.

Additionally, most Americans with diseased cells are black and may not trust a a health system that has often failed provide the most basic preventive and therapeutic care to people suffering from the disease. Some people with diseased cells worry about undergoing medical treatment at the cutting edge of biotechnology.

But for doctors who have spent years watching patients suffer, and for many parents who have watched their children endure years of agony, there is a certain joy in what lies ahead.

“We are finally at the point where we can consider widely available cures for sickle cell disease,” said Dr. John Tisdale, director of the Cellular and Molecular Therapy Branch of the National Heart, Lung and Blood Institute and a member of the advisory committee. .

Dana Jones of San Antonio wants her daughters Kyra, 18, and Kami, 20, to have the chance to benefit from one of the new therapies. Both suffered strokes that left them with learning disabilities – injuries that likely could have been avoided if they had undergone testing and long-known treatment. to prevent nine out of ten strokes in children with the disease. Kyra is now in intensive care as doctors try to control her pain.

Mrs. Jones is overwhelmed by the possibility that her daughters could be cured.

“I pray that Kami and Kyra can be healed of this terrible illness and can finally live truly,” she said.

The cause of the diseased cells has been known for nearly 70 years, but research has lagged, a situation that many believe occurred at least in part because many patients were black and from poor, working-class families .

There are a number of treatments to reduce the impact of diseased cells. Some patients may benefit from a bone marrow transplant which can cure the disease. But that requires finding a donor and, after the transplant, taking medications to prevent the body from rejecting the foreign cells.

In recent years, a number of biotechnology companies have tried new approaches. While Bluebird Bio advances its gene therapy technique, Vertex and CRISPR Therapeutics have focused on the CRISPR-Cas9 gene editing system, which can target specific areas of DNA and turn genes on or off. CRISPR has allowed researchers to disable genes to assess their importance in biomedical research. But until now, it has not been used as a treatment for patients with a genetic disease.

To treat diseased cells, CRISPR cuts a piece of DNA from bone marrow stem cells. This releases a blocked gene to produce a form of hemoglobin that is normally produced only by the fetus. The fetal gene directs the production of hemoglobin which does not give a diseased form. In clinical trials, patients no longer had the complications of sickle cell disease and no longer needed blood transfusions.

But there are concerns that CRISPR could inadvertently cut a piece of DNA in the wrong part of a patient’s genome. This could disrupt a gene and cause blood cancer.

No such problems emerged in clinical trials, but the Vertex trial involved only 44 patients, and only 30 were followed for at least 16 months. The company conducted extensive comparisons of patients’ DNA with that of people in large databases, asking how likely such CRISPR misfires were.

Vertex has announced plans to follow clinical trial patients for 15 years. The company’s data was reassuring enough that the expert committee said Tuesday it saw no reason to suspend the treatment.

There may always be additional studies, noted Alexis Komor, a committee member and professor of chemistry and biochemistry at the University of California, San Diego. But, she said, that would be “expecting perfection at the expense of progress.”

Dr. Joseph Wu of Stanford added: “We all agree that the benefits outweigh the risks. These patients are very sick and this is good therapy.

Scot Wolfe of the University of Massachusetts Chan School of Medicine said: “We want to be careful not to let the perfect be the enemy of the good. »

“There is a huge unmet need,” he added.

Vertex estimates that 20,000 people could be eligible for its treatment and says Medicaid and private insurers have suggested their willingness to pay for it.

“There is almost no way for them to not pay,” said Dr. David Williams, chief of the division of hematology and oncology at Boston Children’s Hospital.

Dr. Williams, who has consulted for Vertex and Bluebird Bio, added that insurers are paying “$3 million apiece” for other gene therapies produced by Bluebird Bio for the diseases thalassemia and adrenoleukodystrophy. With diseased cells and large numbers of black patients, he said, there is an issue of “equity in access and enormous medical needs.”

Some people with the disease may not be eligible, depending on FDA decisions. These could include young children carrying diseased cells and older patients whose bodies have been so damaged that treatment could pose increased risks.

Kevin Wake of Kansas City, Missouri, hopes he’s not too old, at 55, or too damaged. He had three strokes caused by the disease.

Treatments, although curative, are difficult.

Patients first receive eight weeks of blood transfusions, followed by treatment to release bone marrow stem cells into their bloodstream. The stem cells are then collected and sent to companies for processing. Next, patients receive intense chemotherapy to clear their marrow of treated cells. The treated cells are infused back into patients, but they must stay in the hospital for at least a month while the new cells grow and repopulate their marrow.

This treatment “cannot be administered in most hospitals,” said Dr. Alexis Thompson, chief of the division of hematology at Children’s Hospital of Philadelphia, who consults for Vertex.

Another issue is how quickly Vertex can ramp up production. Each patient’s cells must be processed individually in a sterile environment, a daunting prospect.

Stuart Arbuckle, executive vice president and chief operating officer at Vertex, is confident. “We are ready to launch,” he said. But he added that he did not expect a huge surge of patients immediately.

“It’s a pretty big decision for a patient to make,” Mr. Arbuckle said.

One of the patients in the Vertex clinical trial, Marie-Chantal Tornyenu, 22, a senior at Cornell University, said patients also need to be prepared for a “mental adjustment” after treatment.

Ms. Tornyenu said she no longer had the pain attacks that tormented her, especially in high school where she was hospitalized almost every month.

But she spent much of her life taking precautions and worrying about pain and complications from diseased cells. These habits are hard to break.

“It’s a better learning curve after having diseased cells my whole life,” she said. “I still struggle with this mindset: ‘sickle cell disease is you.’ »

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