On February 24, the U.S. Food and Drug Administration (FDA) placed a clinical hold on all LentiGlobin gene therapy trials following an announcement that two participants with sickle cell disease (SCD) developed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), respectively.
While a possible link is still under investigation, the patient reported to have developed MDS after treatment with LentiGlobin may have been prematurely diagnosed, said Philip Gregory, DPhil, chief scientific officer at bluebird bio, the manufacturer of LentiGlobin products. The company was unable to find any cancer cells in the patient’s bone marrow and has asked the FDA for permission to resume clinical trials. In addition, the patient diagnosed with AML was found to carry genetic mutations associated with the disease.
After bluebird bio’s announcement, a separate trial at Boston Children’s Hospital testing a similar treatment using disabled lentivirus to deliver a gene in patients with SCD shut down at the request of the National Institutes of Health (NIH), which had been funding the study. Principal investigator David Williams, MD, said the researchers are now asking NIH to continue the trial.
“These data indeed point away from the vector as causative,” John Tisdale, MD, chief of the cellular and molecular therapeutics branch at the National Heart, Lung and Blood Institute, told The New York Times. However, he added, “researchers still need to better understand the illnesses in the trial participants before they can breathe a final sigh of relief.”