Gene therapy researchers defend trial after death of patient

Jesse Gelsinger died after receiving experimental gene therapy for an inherited liver disease

December 10, 1999
Web posted at: 3:09 a.m. EST (0809 GMT)

In this story: Earlier patient signs not reported, FDA says Father says son would not have wanted trials halted Dispute over research animals RELATED STORIES, SITES

From Medical Correspondent Pete Hartogs

BETHESDA, Maryland (CNN) -- Researchers who led the gene therapy trial that left an 18-year-old man dead have defended their work to government investigators.

Jesse Gelsinger of Tucson, Arizona, died in September after receiving an experimental gene therapy at the University of Pennsylvania for an inherited liver disease.

VIDEO CNN's Eileen O'Connor reports on the gene therapy trial (December 9) Real 28K 80K Windows Media 28K 80K     AUDIO Paul Gelsinger describes his last moments with his son, Jesse 169K/19 sec. AIFF or WAV sound     MESSAGE BOARD Ethics matters: Research risks

The researchers told regulators from the Food and Drug Administration and from the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health that they followed the FDA-approved protocol.

Gelsinger was a participant in the trial conducted by the University of Pennsylvania to study gene therapy for a rare disorder called ornithine transcarbamylase deficiency (OTC), an inherited liver disease that causes life-threatening levels of ammonia to build up in the blood.

The FDA approved the trial with certain restrictions. One of them called for the trial to be stopped if patients suffered serious side effects, all of which were to be reported to the FDA.

On Wednesday, at the start of a three-day meeting investigating what happened in the therapy trial, the FDA accused the researchers of failing to flag reports to the agency of two earlier patients whose tests indicated liver damage that should have stopped the trial.

The FDA also said the researchers did not inform them that Gelsinger's ammonia level was so high that he should have been excluded from the trial on the day they gave him the experimental drug.

The University of Pennsylvania researchers acknowledged they could have called the FDA about the high levels in the two other patients, but said they acted within the agreed-upon protocol.

Paul Gelsinger said earlier this week that his son, Jesse, would not have wanted the experimental trials halted. He described his last moments with his son, saying he developed a fever and other symptoms.

"I'm just an American citizen -- a very concerned one," Gelsinger said.

Dr. Jim Wilson, one of the doctors treating Gelsinger, has said the patient's ammonia levels were being controlled medically. The FDA was kept informed, he said. "Our interpretation of the data made available to the FDA eight months prior to Jesse's therapy and death did not suggest to us that the trial should be modified at that point or halted," Wilson said.

The FDA said the Pennsylvania researchers failed to alert the regulatory agency in a timely manner about data from 11 monkeys, two of which died after receiving the same dose of adenovirus that Gelsinger recieved.

An adenovirus is a common virus used to transport the gene therapy into the body's cells. FDA officials say those data were not presented to them until after Gelsinger died.

The University of Pennsylvania researchers disputed the FDA's version of events. They said only one monkey died, and that it did so only after receiving a dose of adenovirus 17 times higher than what Gelsinger received.

On Thursday, the FDA discussed the possibility of creating a database that would contain results from all adenovirus studies to guide researchers. RAC members expressed concern that no autopsies had been performed on some patients who died during trials as a result of complications perhaps unrelated to the gene therapy.

These and other recommendations will be considered and presented to the director of the NIH next year.

Asked if Gelsinger's death would hinder further gene therapy experiments, Claudia Mickelson, chair of the advisory committee, said, "We have no interest in stopping gene therapy. None whatsoever."

Medical Correspondent Eileen O'Connor contributed to this report.