WASHINGTON _ The worst political and legal aftershocks of thePhase II clinical trial of fialuridine (FIAU) that resulted in the deaths offive people last year are yet to come.A subcommittee of the House Committee on Government Operationsplans to hold public hearings on the FIAU disaster this summer andthree multi-million dollar lawsuits have been filed by patients or theirsurviving relatives as a result of the trial.On May 11, the FDA sent warning letters to National Institutes ofHealth (NIH) researchers and drug companies who conducted theFIAU trials charging that federal regulations were violated. In addition,an advisory committee will report its analysis of the FIAU debacle toNIH Director Harold Varmus at a public meeting on June 2.The cumulative impact of Congressional scrutiny, unprecedented legalactions and intense internal review by government agencies couldchange the conduct of clinical research in this country.FIAU, a nucleoside analog, was originally developed as a treatment forAIDS. Between 1990 and 1993, the NIH conducted three clinical trialsusing the drug. In August 1992, FIAU was licensed by pharmaceuticalgiant Eli Lilly & Co. of Indianapolis from a San Rafael, Calif.-basedbiotechnology company, Oclassen Pharmaceuticals Inc. At the time,Lilly took over responsibility for all reporting activities underOclassen's FIAU investigational new drug application (IND).Although FIAU did not show efficacy in AIDS, it apparently showedpromise as a cure for hepatitis B. As a result, it was tested in 15 chronichepatitis B patients in an NIH Phase II clinical trial that began in March1993 and was terminated in June after several patients experiencedsevere toxicities. Five patients ultimately died as a result of FIAU-related liver failure and two other patients received liver transplants.As the FIAU death toll increased, NIH researchers and Eli Lilly saidthe toxicities were unexpected and could not have been predicted fromearlier studies of the drug. However, an FDA report last November andthe recent warning letters concluded that the researchers repeatedlyignored and overlooked serious toxicities, including four deaths, thatoccurred in earlier trials.Congressional Inquiry To Be ExpeditedRep. Edolphus Towns (D-N.Y.), chairman of the GovernmentOperations Committee's subcommittee on Human Resources andIntergovernmental Relations, has led the Congressional inquiry into theFIAU affair: subcommittee staff have been investigating the matter formonths now. On Friday, the day the FDA released its warning letterspublicly, he pledged to expedite the investigation."FDA's warning letters show that the drug companies and theinvestigators repeatedly and flagrantly violated FDA regulations, studyprotocols and good medical practice," said Towns on May 13. "FDA'scompliance action confirms some of my worst suspicions about theFIAU trials. The drug companies failed the patients. The clinicalinvestigators failed the patients. Where was the NIH during the trials?More importantly, where was the FDA?"Towns called the FDA letters a "slap on the wrist," an assessmentechoed by Sidney Wolfe, director of the Public Citizen's HealthResearch Group in Washington. Wolfe's group has said that FIAUtoxicity results from a Phase I trial in 16 healthy volunteers wereavailable to Eli Lilly before the start of the ill-fated Phase II trial. Twopatients in that trial experienced liver toxicities, one of them washospitalized as a result.Wolfe said the company should have immediately halted all clinicaltrials of FIAU since there was no explanation for liver toxicities inhealthy individuals other than a drug-related adverse event. Instead, thePhase II trial went forward just weeks after the Phase I data wereknown."Lilly has committed a serious, we believe criminal, violation forwhich the FDA has slapped them on the wrist," Wolfe told BioWorld."It sends a message to the drug industry that you can do things whichcause the death of patients and get away with it."Lawsuits FiledThe parents and sister of one FIAU victim, Carlton H. Lee Jr., havejointly filed a $30 million federal claim with the Department of Healthand Human Services (HHS) for "wrongful death" among other things.Lee had served as the Congressional liaison officer for the NationalCommission on AIDS before the FIAU Phase II trial led to his deathfrom liver failure. He was 35 years old.Mike Gloom, an attorney representing the Lee family from theWashington firm of Feldesman, Tucker, Leifer, Fidell and Bank,described Lee as "a pretty healthy guy" who had asymptomatichepatitis when he enrolled in the FIAU study. Lee had asked NIHdoctors to reduce his dose of FIAU in vain and finally discontinued useof the drug on his own.Under federal tort law, individuals suing the government must first filean administrative claim and then wait six months for a response. Ifthere is no response, the plaintiffs are free to file suit in a federaldistrict court.Gloom said the Lee family claim was filed in mid-December. Althoughthe government has not yet responded to the claim, Gloom is hopefulthat a "global settlement" can be reached. A global settlement wouldinvolve Eli Lilly, the U.S. government and possibly other partiespaying a negotiated lump sum. Lilly has already contacted Gloomindependently about a possible settlement. No dollar figure has beennamed. Lilly officials declined to comment on potential litigation.Anne M. McDow, the sister of another FIAU victim, filed suit againstEli Lilly for unspecified compensatory and punitive damages in theU.S. district court for the District of Columbia on Nov. 4 of last year.The suit is a civil action requesting monetary relief arising out of thewrongful death of McDow's brother, a 42-year old architect namedPaul Scott Mertins.Finally, lawyers representing Paul Melstrom, a patient from an earliertrial of FIAU who suffered permanent neuropathies, have filed a $6million claim against HHS and a civil action for unspecified damagesagainst Eli Lilly and Oclassen. Bill Downey, an attorney from the LosAngeles offices of Kananack, Murgatroyd, Baum and Hedlund, toldBioWorld that he hopes the federal government "will acceptresponsibility and allow us to come to a reasonable settlement.""There is no question that the NIH and the companies actednegligently," said Downey. "Even the FDA believes there wasnegligence." Downey said the case is without precedent and will breaknew legal ground. He said that he could find no previous examples oflawsuits filed against the U.S. government for toxicities and deaths dueto investigational drugs.
-- Lisa Piercey Washington Editor
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