FDA Investigates Possible Gene Therapy Contamination

In yet another blow to experimental gene therapy, the Food and Drug Administration said Friday that it has launched an investigation into whether trials at two research centers accidentally exposed young cancer patients to the viruses that cause AIDS and hepatitis C.

The agency also suspended the studies for the treatment of children with brain cancer at St. Jude Children’s Research Hospital in Memphis, Tenn., and Baylor College of Medicine in Houston.

“We are taking this very seriously,” said one FDA official who requested anonymity.

The agency is conducting its own tests on samples of gene-based medicine, which uses a special virus known as an adenovirus to transmit the engineered genes. At issue is whether this virus somehow became contaminated, either through manufacturing or in the laboratory.

Researchers at St. Jude apparently learned through independent testing of the possible problem and notified the FDA on Feb. 4.

The families of the children treated were to have been notified within the last several days, but the FDA official said that none of the patients yet “has been tested for HIV, as far as I know.”

He added: “We are very concerned about the potential impact of this news on parents and families and are working to ensure that they are informed as quickly as possible.”

The children were being treated for neuroblastoma, a brain cancer. The experiment involved removing a patient’s own cancer cells, modifying them with an immune system gene and then inserting them back into the patient to try to stimulate the immune system to attack the cancer.

Many of the children since have died of cancer, the researchers said.

In a statement issued Friday, St. Jude said: “There is no evidence that any of the children who were treated were harmed in any way by the vaccine.”

A Baylor spokeswoman said that the contaminated samples apparently came from St. Jude and that none had been found in the therapy administered to children at Baylor.

The FDA stressed that the findings were preliminary and that the sensitivity of the test used--known as polymerase chain reaction, or PCR--often produces “false positive” results.

The agency, working with the National Institutes of Health, which funds such research, is “not only testing the material but investigating exactly how these clinical trials were conducted,” the FDA official said. It could take up to two weeks before results are available, the FDA said.

An Arizona teenager, who was treated at a program at the University of Pennsylvania last fall, was the first reported death in the gene therapy field.

Federal regulators looking into the death of 18-year-old Jessie Gelsinger of Tucson found numerous violations by university scientists and halted all gene therapy programs being conducted there.

“When Penn reported this death, many people in gene therapy said, ‘It’s just a Penn problem,’ but in my view, where there’s smoke, there is tremendous fire,” said Arthur Caplan, a medical ethicist who heads the Center for Bioethics at Penn. “Gene therapy has been pushing the frontiers hard [and] there are problems.”

Gene therapy researchers, working at what is widely regarded as the cutting edge of treatment for many disorders, attempt to replace or repair damaged or missing genes with healthy ones. Hundreds of gene therapy studies are underway, involving nearly 3,000 patients.

But regulators are taking a fresh look at the field, particularly in the aftermath of revelations by the National Institutes of Health that hundreds of deaths and side effects among patients in gene therapy trials had gone unreported, despite rules that call for the FDA and NIH to be notified.

“We are extremely concerned about some researchers and institutions failing in their responsibility to fully comply with guidelines and regulations,” said another FDA official. “We must be absolutely sure we do not allow the race for effective therapies to undermine patient protections.”

FDA officials emphasized that they are not looking to send a collective chill through the gene therapy research community. “At this point, we’re focused on this particular investigation to determine what went on,” the second FDA official said.

However, he added, “clearly, those who conduct trials and do not follow [rules] do harm to the gene therapy field and other patients who might benefit. . . . It’s important for researchers to take their responsibilities seriously. It’s in everyone’s best interest to comply.”