Gene Therapy Study Is Allowed to Resume
Monday, November 26, 2007
The Food and Drug Administration has given a Seattle company permission to resume its human tests of an experimental, gene-based arthritis treatment whose safety came into question this summer after a 36-year-old study participant died.
Although a final report from outside investigators will not be made public until Dec. 3, the regulatory agency has concluded that the death was not related to the treatment, said a spokeswoman for the company, Targeted Genetics.
"We're very pleased to have the study resume," said the spokeswoman, Stacie Byars. "We think this is a real vindication for gene therapy as a whole."
As many as 35 patients are still eligible to get one more injection of the experimental product, Byars said, adding that the company recognizes that some may opt out because of the death.
The treatment involves the injection of viruses engineered to produce an immune-suppressing protein. The protein helps block the inflammatory process that goes awry in the joints of people with rheumatoid arthritis.
Jolee Mohr, of Taylorville, Ill., died July 24, about three weeks after getting trillions of the genetically engineered viruses injected into her right knee as part of an experiment sponsored by Targeted Genetics. She first became ill the day she got that injection, eventually dying of a fungal infection and massive internal bleeding.
The timing of her death raised the question of whether the treatment contributed to her death.
But investigations by company scientists, a National Institutes of Health expert panel and doctors at the University of Chicago, where Mohr was transferred before she died, found no evidence that the treatment was at fault.
Kyle Hogarth, an intensive-care unit physician at the University of Chicago who cared for Mohr and was involved in the investigation, said yesterday that he feels reasonably certain that the treatment did not kill her. But he is still bothered by the study's design, he said, because it allows participants to keep taking prescription medications that cannot be distinguished from the immune-suppressing protein made by the treatment's gene-modified viruses.
That makes it impossible to fully sort out whether problems that arise during the experiment may be caused by the treatment or the drugs the subjects are taking, he said.
Although conventional arthritis medications can, on rare occasions, make patients especially susceptible to fungal infections, Hogarth and others have questioned whether the gene treatment left Mohr especially defenseless.
"I think they have a horrible design," Hogarth said. "It muddies the picture."
Hogarth also echoed a concern raised by others in the course of the investigation: that Mohr was recruited into the study by her personal physician, who stood to profit from each new patient he enrolled. Medical ethicists have criticized such arrangements as posing a potential conflict of interest.
Contacted by a reporter yesterday, Robb Mohr, Jolee Mohr's widower, said he was unaware that the company had gained permission to resume the study.
"It seems weird that they are allowing it to go ahead, especially on patients who are already taking immune-system drugs," Mohr said. "To me, it is reckless experimentation."
He said he and his lawyers have not yet had substantive talks with the company, pending the release of results from the National Institutes of Health investigation. Those results, which are to be made public at a meeting a week from today, conclude that the engineered viruses do not appear to have replicated in Mohr's body -- an initial concern.
Byars said the protocol for the experiment has been changed. From now on, she said, participants will not be allowed to get an injection of the experimental product if they have a fever, as Jolee Mohr did the day she got her shot.
"We know this has been incredibly tough on the Mohr family," Byars said, "and we again offer our condolences to the family."