The FDA refused to lift the band on gene therapy studies at Penn's Institute for Human Gene Therapy. In a scathing letter to Penn's Institute for Human Gene Therapy on Friday, the U.S. Food and Drug Administration rejected the Institute's defense of its handling of the clinical study that cost an 18-year-old man his life and refused to lift the ban on gene therapy at the University. In the 20-page warning letter addressed to IHGT Director James M. Wilson, who led the study, federal regulators charged the researcher with having "failed to fulfill the obligations as the sponsor" of gene therapy studies, and accused him of violating federal human research regulations. "We are disappointed that the FDA appears to discount a number of the responses to those charges filed by the IHGT," University officials said in a written statement issued Friday. The warning comes six weeks after the FDA charged the Institute with 18 possible violations of federal research protocol breaches and placed a ban on all gene therapy at Penn. IHGT officials responded to the allegations last month and an external committee of scientists is expected to release its findings by mid-April. Federal regulators refuted nearly all of the responses offered by the Institute concerning the gene therapy trial in which Jesse Gelsinger, who died last September, was enrolled.Wilson and his researchers later determined that Gelsinger died of multiple organ failure induced by the gene therapy. The Institute -- which until recently had been considered one of the top gene therapy research centers in the world -- now has 15 business days to inform the FDA about any corrective steps that will be taken and submit any data and documentation for which the letter calls. But a source close to the investigation said that the University will now only submit the documents asked for in the letter; it will not seek to dispute every point with the FDA. "We will not reiterate our position on all of those points that state that we don't agree with [the FDA]," the source said, adding that the University will now await the FDA's final decision on gene therapy at the University, whether it be a lifting of the six-week-old ban or a continued or permanent suspension. University spokesman Ken Wildes said Penn officials could not speculate about the FDA's next move. FDA spokesman Larry Bachorik said the warning letter represents a major attack on Wilson's credibility as a gene therapy researcher. "Warning letters are issued only for serious violations," he explained. He added that the fact that the FDA issued Wilson such a letter "suggests that we had serious concerns" about Wilson's ability to conduct gene therapy research. "I think it's fair to say that the FDA disagreed with many of the responses," Bachorik said. "We take these violations very seriously, and we will closely monitor the response." While the letter is directed specifically to Wilson in his capacity as head of the Institute, the source said he expects Wilson and the two other principal researchers of the trial -- Steven Raper and Mark Batshaw -- to receive similar letters by Wednesday, which would "take them to task as investigators." Neither Wilson, nor Medical School Senior Vice Dean Richard Tannen, who has spoken for IHGT in the past, were available for comment, according to Wildes. Lee Silver, a professor of Molecular Biology and public affairs at Princeton University, said it's unlikely that this marks the end of gene therapy at Penn. "I think mediation will take place and all the deficits in the protocols will be corrected, and it will come back," he said. In the letter, the FDA maintained its position that patients were not properly informed about the dangers posed by the gene therapy trial. The letter stated that patients were unaware of prior adverse events in the trial, and cited numerous cases of poor documentation. Another issue that the FDA raised in the letter was that the IHGT failed to notify regulators of the deaths of two laboratory monkeys and the liver toxicity of a third until one year after the trial was completed. IHGT officials had maintained that the two monkeys were enrolled in studies unrelated to the Gelsinger case, and that the third -- though on a study very similar to the OTC study -- received a dosage of genes far greater than what OTC patients received. But regulators insisted that researchers "had an affirmative obligation" to notify the FDA about the monkey results. The FDA also reasserted its claim that many patients -- Gelsinger included -- were ineligible to participate because of high blood ammonia levels. In its response to the FDA, Wilson's researchers explained that though Gelsinger's ammonia level was high prior to infusion, previous readings were within protocol limits. But the FDA letter insisted that IHGT researchers should have waited to see if Gelsinger's ammonia levels would have decreased before proceeding.Comments powered by Disqus
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