Patients with sickle cell disease urge FDA to greenlight landmark gene-editing treatment

About a dozen people who have sickle sickle cell disease or relatives with the debilitating blood disorder implored the Food and Drug Administration on Tuesday to approve a revolutionary gene editing treatment — created by CRISPR Therapeutics and Boston-based Vertex Pharmaceuticals — that those who received it in a clinical trial said transformed their lives.Erin Clark/Globe Staff

About a dozen people who have sickle cell disease or relatives with the debilitating blood disorder implored the Food and Drug Administration on Tuesday to approve a revolutionary gene editing treatment that those who received it in a clinical trial said transformed their lives.

Victoria Gray, 38, who in 2019 became the first patient to have the DNA of her damaged blood cells edited with the Nobel Prize-winning technology called CRISPR, told an FDA advisory committee that the excruciating pain that dominated her life is gone.

“After receiving this treatment, I no longer have pain,” said Gray, her voice cracking with emotion. “I no longer have hospital stays or receive blood transfusions. I now work full time.”

The treatment, called exa-cel and administered with a single infusion, was created by Boston-based Vertex Pharmaceuticals and CRISPR Therapeutics, which is headquartered in Switzerland but has most of its employees in Massachusetts.

The FDA doesn’t dispute exa-cel’s benefits. But the seven-hour hearing didn’t end with a customary vote by the advisory committee on whether to recommend a treatment for approval.

Instead, the FDA sought feedback about the scientific methods that Vertex and CRISPR used to evaluate the risk of inadvertently changing patients’ DNA beyond the targeted disease — so-called off-target editing.

Dr. Daniel E. Bauer, a trial investigator who works at Dana-Farber Cancer Institute and Boston Children’s Hospital, said exa-cel contains hundreds of millions of edited cells and one could undoubtedly go off target and cause leukemia. He described the risk as “modest” given the benefits of the treatment, but added, “We need to be humble and open to learning from these brave patients.”

The FDA is expected to decide whether to approve exa-cel by Dec. 8. Michael Abrams, a senior researcher in Public Citizen’s Health Research Group, called on regulators to delay approval until more studies could be conducted.

But one member of the advisory committee, said delay was unwise, given the damage sickle cell causes. “The evidence of the efficacy of this treatment is overwhelming,” said Lisa M. Lee, associate vice president for research and innovation at Virginia Tech

Vertex executives also downplayed the health risks.

“We designed exa-cel to minimize off-target editing risks,” said Vertex chief scientific officer David Altshuler, who cited three company studies that found no evidence of mistaken edits in the genes of patients who received the treatment.

Vertex Pharmaceuticals chief scientific officer David Altshuler.David L. Ryan/Globe Staff

Christopher Simard, the company’s vice president of medical safety and risk management, said Vertex will study patients for 15 years if the FDA approves the treatment. “We will closely monitor these patients for safety signals over the long term,” he said.

Sickle cell disease ― which causes crushing pain, damages organs and joints, and cuts lives short ― has eluded effective treatments longer than a number of other genetic diseases. The disorder mostly affects people of color, and many experts attribute the slower progress in developing effective medicines to structural racism, especially in funding for research. An estimated 100,000 Americans suffer from sickle cell.

Vertex and CRISPR have competition from another local drug maker seeking to market a novel sickle cell treatment. Bluebird Bio of Somerville, has developed a promising gene therapy that the FDA is scheduled to consider for approval by Dec. 20.

Both treatments have generated extraordinarily promising results in clinical trials. Some scientists even say these medicines could cure the disease, although others say that conclusion is premature.

Several sickle cell specialists, however, worry about the cost of the treatments ― and the resulting impact on federal and private insurance plans. Each medicine is expected to cost at least $1 million to $2 million, not including the expense of administering the one-time infusions and other aspects of the treatments.

Nonetheless, the Institute for Clinical and Economic Review, or ICER, an independent Boston-based drug-pricing watchdog, said the treatments would be worth the expense, given the cumulative costs of treating sickle cell over a lifetime and the benefits that the new approaches would bring to patients and families.

Sickle cell is a group of inherited blood disorders that affect hemoglobin, the oxygen-carrying protein in red blood cells. It occurs in about one of 365 Black births in the United States, and one of 16,300 Hispanic American births, according to the Centers for Disease Control and Prevention. Millions of people worldwide have the condition. White people are rarely diagnosed with it.

The disease causes round, flexible red blood cells to deform into a sickle shape and stick to vessel walls. That deprives tissues of oxygen, often necessitating blood transfusions. A 2019 study in JAMA Network Open estimated the life expectancy of adults with sickle cell in the United States is 54 years, about 20 years shorter than the general population.

People with sickle cell inherit two faulty hemoglobin genes ― one from each parent. If someone inherits just one defective copy, that person is said to have sickle-cell trait but can lead a normal life.

A US Food and Drug Administration building is seen behind FDA logos at a bus stop on the agency's campus in Silver Spring, Md., on Aug. 2, 2018. Jacquelyn Martin/Associated Press