The U.S. Food and Drug Administration last month rejected a letter of explanation by Dr. James M. Wilson, director of Penn’s Institute for Human Gene Therapy (IHGT), concerning allegations that he violated safety procedures in a clinical gene-therapy trial that resulted in the death of 18-year-old Jesse Gelsinger in 1999. Saying that his written explanations “fail to adequately address the violations,” the FDA offered him a regulatory hearing to determine whether he will be “entitled to receive investigational new drugs.” As the Gazette went to press last month, it was not known whether he would participate in such a hearing.
Wilson’s letter to the FDA, written last March, was a response to charges that he had “repeatedly and deliberately violated federal regulations” as an investigator in clinical trials using human subjects—and to being informed that proceedings were being instituted to prevent him from conducting further genetic testing on human subjects [“Gazetteer,” March/April 2001].
Gelsinger suffered from a hereditary liver disorder known as ornithine transcarbamylase deficiency (OTCD), which prevents the liver from properly processing ammonia. Scientists at the IHGT had developed a technique for delivering corrective genes into the liver through an injection of a modified cold virus, but several days after receiving the drug in September 1999, Gelsinger died of acute-respiratory-distress syndrome and multiple-organ failure.
After the FDA found “numerous serious deficiencies” in the oversight and monitoring of the OTCD trial, Wilson and the researchers at the IHGT acknowledged certain lapses in protocol, but argued that those lapses did not contribute to Gelsinger’s death. In September 2000, the Gelsinger family filed a lawsuit against the University, Wilson, and several other scientists connected with the incidents; six weeks later, the case was settled out of court.
“This most recent letter is a continuation of the administrative procedures that were begun by the FDA two years ago,” said Wilson, the John Herr Musser Professor and Chair of Molecular and Cellular Engineering, in a statement. “I will continue a dialogue with the FDA in an effort to reach a resolution satisfactory to all parties.”
In his letter to Wilson, Dennis E. Baker, the FDA’s associate
commissioner for regulatory affairs, said that the agency’s offer to enter into a consent agreement “remains open.” No final decision has been made on Wilson’s eligibility to continue using “investigational drugs,” Baker added.
