By Lisa Seachrist
WASHINGTON ¿ The Food and Drug Administration issued a warning letter to University of Pennsylvania gene therapy researcher James Wilson for failure to fulfill his obligations as the sponsor of studies with investigational products, and for violating FDA regulations in the conduct of the gene therapy clinical trial that resulted in the death of Jesse Gelsinger.
Gelsinger was a participant in a Phase I gene therapy study for patients with ornithine transcarbamylase deficiency (OTCD). He died days after receiving a hepatic infusion of an altered adenoviral vector.
The agency¿s letter, dated Friday, deals only with Wilson¿s activities as sponsor of the study and states the researcher will receive an additional letter addressing his activities as a clinical investigator in the study. Wilson, as director of the Institute for Human Gene Therapy (IHGT) at Penn, is responsible for ensuring that IHGT fulfilled all of its obligations as sponsor of gene therapy trials.
Wilson and Penn have 15 business days to detail the steps the institute has taken and will take in order to correct the violations detailed by FDA. Until the violations have been corrected, all gene therapy trials sponsored by IHGT will remain on clinical hold.
The agency¿s warning letter largely confirms the observations reported in its Jan. 18 inspection of IHGT. The university later replied to those observations. (See BioWorld Today, Feb. 22, 2000, p. 1.)
The University of Pennsylvania issued a statement in response to the warning letter later Friday, noting it takes the FDA¿s charges ¿extremely seriously,¿ but is ¿disappointed that the FDA appears to discount a number of the responses to those charges filed by the IHGT three weeks ago.¿
The agency said Wilson, as sponsor, failed to immediately report the occurrence of adverse reactions in violation of the written protocol agreement, failed to submit protocol amendments, and failed to incorporate agreed upon protocol changes into the protocol. In addition, the agency took issue with IHGT¿s failure to report the results of a study using adenoviral vector in monkeys. Monkeys receiving the same vector used to treat the patients in the OTCD gene therapy study experienced liver failure and some developed disseminated intravascular coagulation, the event that led to Gelsinger¿s death.
The agency also brought up issues with the informed consent procedures for the trial, the phrasing of the informed consent document, and the eligibility criteria for the study.
FDA maintained Wilson and IHGT failed to fulfill the general responsibilities of sponsors by lacking standard operating procedures (SOPs) to conduct a clinical study. Penn acknowledged it lacked SOPs in its Feb. 14 response and promised to develop clinical trial SOPs by April 6. In addition, Penn has hired a contract research organization to oversee the conduct of clinical trials at IHGT. The agency has requested more information about the implementation of SOPs and the role of the contract research organization.
The letter said Wilson may still face judicial proceedings or administrative actions concerning these violations.