FDA Halts Human Gene Research at University
The Food and Drug Administration called a halt to human gene therapy research at the University of Pennsylvania on Friday after an investigation into the death in September of an 18-year-old patient found numerous violations by university scientists.
The inquiry found serious lapses by the study’s principal researchers in reporting potentially serious side effects--seen before the patient died--and in other procedures involving entry criteria and informed consent.
The action effectively stops seven studies underway at the University of Pennsylvania’s Institute of Gene Therapy, in addition to the trial in question, which was suspended after the death.
Dr. Philip Noguchi, an FDA official involved in the oversight of gene therapy research, said that the studies would not be allowed to resume until the institute and the principal investigator, Dr. James M. Wilson, correct the violations and demonstrate that their procedures comply with FDA rules.
In response to the FDA action, University of Pennsylvania President Judith Rodin said that she had asked the school’s provost to appoint a committee of “distinguished scientists with extensive experience in clinical research,” but without affiliation to the university, to review the institute’s oversight and monitoring procedures and recommend corrections.
The university, she said, “has cooperated fully with all aspects of the FDA’s investigation and would continue to do so.”
Jesse Gelsinger of Tucson had volunteered for the experimental treatment with the hope of curing his rare genetic disorder, ornithine transcarbamylase deficiency, which prevents the liver from breaking down ammonia, a normal byproduct of protein digestion.
He died after researchers infused a genetically modified virus into his liver in an attempt to introduce new genes that could correct those responsible for his ailment.
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. More than 300 gene therapy studies are underway, and at least 2,500 patients have been treated without apparent harm.
While Gelsinger was not the first patient undergoing gene therapy to die, his death is believed to be the first directly related to the experimental procedure.
In its findings, the FDA said that two earlier volunteers in the University of Pennsylvania study suffered reactions serious enough to have put the study on hold. But researchers, the FDA found, attributed the side effects to the patients’ medical histories rather than the experiment.
Also, the scientists did not report the deaths of two monkeys under treatment during animal studies, which typically precede human trials.
The agency also said that Gelsinger’s blood levels of ammonia, a measure of liver damage, were too high for him to have been eligible for the study and that scientists had altered eligibility criteria without FDA approval.
Finally, the agency faulted the lab for not properly monitoring the study--saying that it did not have an overall standard operating procedure for its clinical trials. It also said that it found irregularities in the forms on which researchers are supposed to explain the possible risks and benefits of participation and on which patients consent to take part.
Noguchi said that, while most gene therapy studies are being done in “a responsible manner,” the agency is considering stepping up its inspections and “reminding investigators of their responsibilities.”
