November 29, 2022

Just weeks after promising sickle cell disease gene therapy appeared to hit a roadblock, the outlook for treatment is now looking brighter. Preliminary data suggesting it could cause cancer has not held up.

In gene therapy, scientists insert a normal gene into the patient’s DNA to correct sickle cell disease caused by a devastating mutation. The cutting-edge treatment could prove to be a cure, and a company testing the treatment, Bluebird Bio, was on track to apply for approval from the Food and Drug Administration next year.

However, on February 16, Bluebird Bio announced that a sickle cell patient treated in a clinical trial five years ago had developed acute myeloid leukemia. Another patient developed acute myelodysplastic syndrome, a form of cancer that is often a precursor to leukemia.

The company stopped its studies of sickle cell patients and those with another blood disorder called beta thalassemia while its researchers tried to understand whether gene therapy was flawed.

On Wednesday, Bluebird Bio reported that it had found no evidence that gene therapy caused the sickle cell patient’s leukemia.

The gene inserted into the patient’s DNA did not interfere with the function of other genes, the company said. And the gene wasn’t inserted into the genome near anyone else known to be involved in leukemia.

Bluebird Bio is still investigating whether its treatment is related to acute myelodysplastic syndrome, but officials have asked the Food and Drug Administration to allow their clinical trials to continue.

A separate sickle cell study at Boston Children’s Hospital was also discontinued when Bluebird Bio announced the two cancers at the request of the National Institutes of Health, which is paying for the study.

Dr. David Williams, a hematologist at Boston Children’s and lead researcher on the study, said the researchers are asking permission from the NIH to resume their work.

Like Bluebird Bio investigators, Dr. Williams and his colleagues used a disabled lentivirus to deliver a gene to sickle cell patients. Lentiviruses are considered safe – hundreds of patients in other gene therapy studies have been treated with them and no blood cancers have been reported. The possibility that lentiviruses may not be safe was a matter of great concern.

The leukemia patient in the Bluebird Bio study had genetic abnormalities related to leukemia, which could explain why they developed.

Philip Gregory, the company’s chief scientist, said it was not yet clear whether the patient diagnosed with myelodysplastic syndrome actually had it. So far, Bluebird Bio has not been able to find any cancer cells in its bone marrow.

“He may have been diagnosed prematurely,” said Dr. Gregory. If cancer cells are found in the patient’s marrow, the company will perform the same detailed molecular analysis it did for the leukemia patient, added Dr. Gregory added.

Dr. John Tisdale, director of cellular and molecular therapeutics at the National Heart, Lung and Blood Institute, was cautiously optimistic.

“These data actually dismiss the vector as causal,” he wrote in an email. He added that the researchers need a better understanding of the study participants’ illnesses before they can exhale one last sigh of relief.