RAC meeting learns of gene therapy improprieties occurring prior to student's death

December 09, 1999

Dec 9, 1999RAC meeting learns of gene therapy improprieties occurring prior to student's deathThe FDA confirmed to members of the press attending this week's Recombinant DNA Advisory Committee (RAC) meeting that it has preliminary evidence that researchers at the University of Pennsylvania committed important deviations from protocol in their gene therapy trial. As reported in theWashington Post,1these deviations may have contributed to the death of 18-year old Jesse Gelsinger, the first reported gene therapy-associated death. However, Paul Gelsinger, Jesse's father, warned reporters that the FDA's announcement is simply an attempt to divert attention from the FDA's own unethical behavior in overseeing the safety of gene therapy trials.The University of Pennsylvania trial was a pilot study of adenovirus-mediated gene therapy for ornithine transcarbamylase (OTC) deficiency. It involved 18 patients and tested incremental doses of the viral vector + transgene. According to Kathryn Zoon, Director of the Center for Biologics Evaluation and Research at the FDA, the Pennsylvania researchers appear not to have followed FDA-regulated protocol at 3 points in the trial: (a) the researchers treated Jesse Gelsinger despite the fact that following his enrollment in the trial Jesse's ammonia levels rose above the acceptable threshold for inclusion in the study; (b) though 4 patients treated at a lower dose than Jesse experienced grade 3 toxicity, the researchers drew only 2 of the cases adequately to the attention of the FDA and did not halt the trial; (c) the researchers did not submit certain animal safety study results to the FDA within the time required of them."These deviations would impact on whether or not the participant [Jesse Gelsinger] would have been treated in the first place, so from that point of view they are important," said Zoon. When asked what sanctions were to be taken against the researchers and whether criminal charges were a possibility, Zoon was cautious. "It is important to find out what the deviations were, who was involved, who was responsible," she said, but conceded that "there could be a wide range of options from administrative to the most severe, which could be criminal."THE RESEARCHER SPEAKSDr James M Wilson (University of Pennsylvania), who headed the OTC gene therapy study, reserved his public comments on the trial for Wednesday's official RAC meeting. However, Wilson did join the RAC press conference following the departure of the FDA representatives and read a statement to the press. He defended his research team against the FDA's first two charges. While he referred positively to his past and continued cooperation with the FDA, he noted, "We are disappointed that the FDA has apparently decided prior to the presentations scheduled for [Wednesday] to publicly disclose what they have characterized as "preliminary findings".THE BEREAVED FATHER SPEAKSMeanwhile, Paul Gelsinger, the father of the deceased Jesse Gelsinger, made a surprise appearance at the end of the press conference. In an impassioned speech, Paul Gelsinger accused the FDA of "trying to divert attention from the real ethical issue going on". Early this week, he explained, he had spoken with the FDA and accused them of bowing to industry in not implementing a gene therapy information network planned 5 years ago, a network which would have tracked patients involved in gene transfer trials. He warned the FDA that he would report this to the press. He quoted minutes from the RAC meeting of June 8-9, 19952in which Dr Philip Noguchi, Director of Cellular and Gene Therapies at the FDA, is quoted as saying, in discussing impediments to the realization of the FDA-funded information network, "that his superiors answer to industry", to which RAC committee member Alexander M Capron (University of Southern California) responded "that he thought the FDA answers to the American people."According to Paul Gelsinger, the internet-based network would have helped to coordinate the efforts of the NIH, the RAC, and the FDA and would have improved the reporting and dissemination of information on adverse events in gene therapy. These are the very things that are being addressed at this week's RAC meeting, too late for Jesse Gelsinger.Kat RotherCited sources1. Rick Weiss, Deborah Nelson. Methods faulted in gene test death.Washington Post,December 8, 1999, page A012. Minutes of meeting. Recombinant DNA Advisory Committee, Department of Health and Human Services, National Institutes of Health. Washington DC, June 8-9, 1995Thu, 09 Dec 1999 16:50:57

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