Gene therapy researchers are breathing easier after a company reported today that the modified virus it used to treat sickle cell disease in a person who later developed leukemia was very unlikely to have caused the cancer.
The leukemia case, which Bluebird Bio disclosed on 16 February, led the company to halt its two sickle cell disease trials and suspend sales of a similar treatment for beta-thalassemia. The following week, the U.S. Food and Drug Administration (FDA) put a hold on the company’s two sickle cell disease trials and two beta-thalassemia trials.
But the company has now done various lab tests and found “important evidence demonstrating that it is very unlikely our BB305 lentiviral vector played a role in this case,” said Chief Scientific Officer Philip Gregory in a press release. The company is now in discussions with FDA about lifting the trial hold.
The studies use a modified virus called a lentivirus to insert a curative gene into the chromosomes of patients’ blood stem cells. About 2 decades ago, a different viral vector was tested to treat the blood stem cells of patients with an inherited immune disorder, and several later developed leukemia as a result.
This did not happen in the sickle cell trial, Bluebird suggests. The company had reported on 25 February that the patient’s leukemia cells had mutations and other changes in some known leukemia genes, suggesting these changes—which are typical in leukemia—contributed to the cancer.
That didn’t completely rule out a role for the lentiviral vector, which the company had said earlier inserted its DNA into the patient’s leukemia cells. But today the company reports that the gene where that DNA landed, VAMP4, plays no known role in cancer. Moreover, the DNA inserted into VAMP4 did not turn on or off any nearby genes, tests showed.
Gene therapy researcher Donald Kohn of the University of California, Los Angeles, agrees with the company’s conclusion. There is “no evidence that the integrant was affecting expression of any genes near its integration site,” says Kohn, who is one of several academic researchers who consulted with Bluebird. That makes the case “quite different” from the cases years ago. (Bluebird is paying Kohn for his time, but he says that didn’t influence his opinion.)
Bluebird had also reported that a different patient had developed a preleukemic condition called myelodysplastic syndrome (MDS). But the company has walked back that concern. It now says the person had some possible signs—anemia and an extra chromosome in some bone marrow cells—but did not turn out to have abnormal bone marrow cells that would indicate MDS.