A groundbreaking treatment for sickle cell disease is safe enough for clinical use, a panel of experts said Tuesday, pushing federal approval by Dec. 8 for a powerful potential cure for the disease that afflicts more than 100,000 Americans. is likely to.
The Food and Drug Administration had previously found that the treatment, known as Exa-Cell and jointly developed by Boston’s Vertex Pharmaceuticals and Switzerland’s CRISPR Therapeutics, was effective. The panel’s findings Tuesday about the safety of Exa-Cell send it to the FDA for a decision on whether to greenlight it for widespread patient use.
Exa-Cell frees patients from the debilitating and painful effects of this chronic, deadly disease. If approved, the Vertex product would be the first drug to treat a genetic disease with CRISPR gene-editing technology.
It could also be the first of a series of new options to cure the painful disease. By Dec. 20, the FDA will decide on a second potential treatment for sickle cell, a gene therapy developed by Bluebird Bio, a Somerville, Mass., company.
Sickle cell disease is caused by a gene mutation that causes blood cells to become misshapen, causing them to look like sickles or crescents. It affects millions of people worldwide, the majority of whom are of African descent. The deformed cells become trapped in the blood vessels, leading to strokes, organ damage and excruciating pain as the muscles become deprived of oxygen.
The effects of sickle cell disease start early in life. Evelyn Islam of Milwaukee, now 8, had 22 blood transfusions and had 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 people the new gene therapy 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 Marcus deal with sickle cell symptoms. When she had a hip replacement in 2018, her father took time off from his job to help care for her.
“And that’s just us,” she said.
Marcus died in 2020 at the age of 36 from a stroke caused by sickle cell.
New treatments like the one approved Tuesday are expected to cost millions of dollars per patient, though Vertex has not yet disclosed how much it will charge. But lifelong care for patients with the disease is also extremely expensive, causing an estimated loss to the health care system. $3 billion per year,
It’s not yet clear how many people will seek the new therapy. The new therapy is also not easy to tolerate and brings difficulties for patients, who must undergo chemotherapy and spend more than a month in the hospital. Family members are also affected – they may need to take time off work during the most intensive phase of treatment.
Additionally, the majority of Americans with sickle cell are black and may not believe it Health care system that has often failed To provide the most basic preventive and therapeutic care for people suffering from disease. Some people with sickle cell are concerned about undergoing medical treatment at the cutting edge of biotechnology.
But for doctors who have watched patients suffer for years, and many parents who have watched their children suffer for years, they are happy with what’s to come.
“We are finally at a place where we can envision a widely available treatment for sickle cell disease,” 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. Are.” ,
Dana Jones of San Antonio wants her daughters Kyra, 18, and Kami, 20, to have a chance at one of the new therapies. Both had strokes that left them with learning disabilities – injuries that probably could have been avoided if they had been given long-known screening tests and treatment. To prevent nine out of 10 strokes In children suffering from the disease. Kyra is now in intensive care as doctors try to control her pain.
Ms. Jones is overwhelmed by the possibility that her daughters can be cured.
He added, “It is my prayer that Kami and Kiara will recover from this terrible disease and finally be able to live a truly fulfilling life.”
A new treatment and a new technology
The cause of sickle cell has been known for nearly 70 years, but research lagged, with many saying the condition arose at least partly because so many patients were black and from poor and working-class families.
There are several treatments to reduce the effects of sickle cell. Some patients are able to undergo a bone marrow transplant which can cure the condition. But it requires finding a donor and taking medications to prevent the body from rejecting the foreign cells after the transplant.
In recent years, many biotechnology companies have tried new approaches. While Bluebird Bio is advancing its gene therapy technology, Vertex and CRISPR Therapeutics have focused on the gene-editing system CRISPR-Cas9, which can enter specific regions of DNA and turn genes on or off . CRISPR has allowed researchers to inactivate genes to assess their importance in biomedical research. But till now it has not been used as a treatment for patients with genetic diseases.
To treat sickle cell, CRISPR cuts a piece of DNA in bone marrow stem cells. This releases the blocked gene to make a form of hemoglobin that is normally only produced by the fetus. The fetal gene directs the production of hemoglobin, which is not sickle-shaped. In clinical trials, patients no longer had complications from sickle cell disease and did not require blood transfusions.
But there is concern that CRISPR might inadvertently cut a piece of DNA in the wrong part of the patient’s genome. It can disrupt a gene and cause blood cancer.
No such issues have emerged in clinical trials, but the Vertex trial included only 44 patients, and only 30 were followed for at least 16 months. The company conducted an extensive comparison of the patients’ DNA with the DNA of people in large databases and asked how likely such CRISPR misfires might be.
Vertex said it plans to follow clinical trial patients for up to 15 years. The company’s data were convincing enough that the expert committee said Tuesday it saw no reason to stop the treatment.
Noted committee member Alexis Komor, a professor of chemistry and biochemistry at the University of California, San Diego, said there could always be additional studies. But, he said, this would be “expecting perfection at the expense of progress”.
“We all agree that the benefits outweigh the risks,” said Stanford’s Dr. Joseph Wu. These patients are very sick and this is a good therapy.”
“We want to be careful not to let the perfect become the enemy of the good,” said Scott Wolfe of the University of Massachusetts Chan Medical School.
“There is a huge need that is unmet,” he said.
If it’s safe, who gets it?
Vertex estimates that 20,000 people may be eligible for its treatment, and says Medicaid and private insurers have suggested a willingness to pay for it.
“There’s almost no way they can do that No Pay up,” 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, said insurers pay “$3 million a pop” for other gene therapies produced by Bluebird Bio for the diseases thalassemia and adrenoleukodystrophy. With sickle cell and its large number of black patients, there is an issue of “equity in access and tremendous medical need,” he said.
Depending on FDA decisions, some people with this disease may not be eligible. These may include young children with sickle cell and older patients whose bodies are so damaged that treatment may increase the risk.
Kansas City, MO. Kevin Wake hopes he’s not too old, 55, or too damaged. Due to this disease he has suffered three strokes.
Treatments, while curative, are difficult.
Patients first receive blood transfusions for eight weeks, then undergo treatment to release bone marrow stem cells into their bloodstream. The stem cells are then removed and sent to companies for treatment. Next, patients receive intensive chemotherapy to clear the marrow of the treated cells. The treated cells are put back into the patients, but they have to stay in hospital for at least a month while the new cells grow and replenish their marrow.
That treatment “can’t be given at most hospitals,” said Dr. Alexis Thompson, chief of the hematology department at Children’s Hospital of Philadelphia, who consulted for Vertex.
Another issue is how fast Vertex can ramp up production. Each patient’s cells must be treated individually in a sterile environment, which is a daunting prospect.
Stuart Arbuckle, Vertex’s executive vice president and chief operating officer, is confident. “We are ready to launch,” he said, but added that he did not expect such a large number of patients to arrive immediately.
“This is a huge decision for any patient,” Mr. Arbuckle said.
One of the patients in the Vertex clinical trial, Marie-Chantal Tornienu, 22, a senior at Cornell University, said patients also need to be prepared for a “mental adjustment” after treatment.
Ms. Tornieanu said she no longer has the pain problems that plagued her, especially in high school when she had to be hospitalized almost every month.
But she has spent most of her life taking precautions and worrying about the pain and complications from sickle cell. Those habits are hard to break.
“This is one of the biggest opportunities I’ve had in my entire life to learn from sickle cell,” he said. “I still struggle with that mentality – ‘Sickle cell is you.'”