Panel says innovative sickle cell cure safe enough for patients | ET REALITY


A panel of experts said Tuesday that an innovative treatment for sickle cell anemia was safe enough for clinical use, setting the stage for likely federal approval by Dec. 8 of a powerful potential cure for a disease that affects more of 100,000 Americans.

The Food and Drug Administration had previously found that the treatment, known as exa-cel and jointly developed by Vertex Pharmaceuticals of Boston and CRISPR Therapeutics of Switzerland, was effective. Tuesday’s panel’s conclusion on the safety of exa-cel sends it to the FDA for a decision on whether to authorize it for widespread use in 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 of a series of new options to cure this painful disease. By Dec. 20, the FDA will decide on a second potential cure for sickle cell anemia, a gene therapy devised by the Somerville, Massachusetts, company Bluebird Bio.

Sickle cell disease is caused by a genetic mutation that causes blood cells to become deformed so that they look like sickles or crescents. It affects millions of people around the world, the majority of whom are of African descent. The misshapen cells become stuck in blood vessels, causing strokes, organ damage and bouts of agonizing pain as muscles starve of oxygen.

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

But for many the new gene therapies will arrive 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 symptoms of sickle cell anemia. When she had a hip replacement in 2018, her father ended up taking a layoff from her job to help care for her.

“And that’s just us,” he said.

Marqus died in 2020, at age 36, from a stroke caused by sickle cell anemia.

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 will charge. But lifelong care for patients with this disease is also enormously expensive, costing the health system approximately 3 billion dollars a year.

It’s not yet clear how many people will seek out the new therapy. The new therapies are also not easy to tolerate and pose difficulties for patients, who will have to undergo chemotherapy and spend more than a month in the 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 sickle cell anemia are black and may not trust Health system that has often failed. to provide the most basic preventative and therapeutic care to those suffering from the disease. Some people with sickle cell anemia are eager to undergo medical treatment that is on the cutting edge of biotechnology.

But for doctors who have spent years watching patients suffer, and for many parents who have seen their children endure years of agony, there is joy in what awaits them.

“We are finally at a point where we can imagine widely available cures for sickle cell anemia,” said Dr. John Tisdale, director of the cellular and molecular therapeutics branch at 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 opportunity to do one of the new therapies. Both suffered strokes that left them with learning disabilities, injuries that likely could have been avoided if they had been screened and treated with long-known treatment. to prevent nine out of 10 strokes in children with the disease. Kyra is now in intensive care as doctors try to manage her pain.

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

“It is my prayer that Kami and Kyra can be cured of this terrible disease and can finally live truly,” he said.

The cause of sickle cell anemia has been known for almost 70 years, but research was delayed, a situation that many say occurred at least in part because many patients were black and came from poor and working-class families.

There are several treatments to reduce the impact of sickle cells. Some patients can receive bone marrow transplants that can cure the condition. But that requires finding a donor and, after the transplant, taking medications to prevent the body from rejecting the foreign cells.

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

To treat sickle cell anemia, CRISPR cuts a piece of DNA from bone marrow stem cells. That releases a blocked gene to produce a form of hemoglobin that is normally only produced by the fetus. The fetal gene directs the production of hemoglobin that does not take the sickle shape. In clinical trials, patients no longer had the complications of sickle cell anemia 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. That could alter a gene and cause blood cancer.

No such problems have arisen in clinical trials, but only 44 patients participated in the Vertex trial, and only 30 were followed for at least 16 months. The company made extensive comparisons of patients’ DNA with that of people in large databases asking how likely such CRISPR flaws might be.

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

There can always be additional studies, said committee member Alexis Komor, a professor of chemistry and biochemistry at the University of California, San Diego. But, he 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 quite 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 a willingness to pay for it.

“There is almost no way they can No pay,” said Dr. David Williams, chief of the division of hematology and oncology at Boston Children’s Hospital.

Dr. Williams, who has been a consultant for Vertex and Bluebird Bio, added that insurers pay “$3 million each” for other gene therapies produced by Bluebird Bio for the diseases thalassemia and adrenoleukodystrophy. With sickle cell anemia and its large number of black patients, he said, there is a question of “equity in access and tremendous medical need.”

Some people with the disease may not be eligible, depending on FDA decisions. They could include young children with sickle cell anemia and older patients whose bodies have been so damaged that the treatment could pose greater risks.

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

The treatments, although curative, are difficult.

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

That 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 treated individually in a sterile environment, an arduous prospect.

Stuart Arbuckle, executive vice president and chief operating officer of Vertex, is confident. “We’re ready to launch,” he said. But he added that he didn’t expect a large surge of patients right away.

“This is a pretty big decision for a patient,” Arbuckle said.

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

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

But he has spent much of his life taking precautions and worrying about the pain and complications of sickle cell anemia. Those habits are hard to break.

“It’s a big learning curve having had sickle cell anemia my whole life,” she said. “I’m still struggling with that mentality: ‘Sickle cell is you.’”

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