Roanoke Times
                 Copyright (c) 1995, Landmark Communications, Inc.

DATE: WEDNESDAY, September 1, 1993                   TAG: 9309010008
SECTION: NATIONAL/INTERNATIONAL                    PAGE: A-4   EDITION: METRO 
SOURCE: Associated Press
DATELINE:                                 LENGTH: Medium

5TH PERSON DIES IN CLINICAL TRIAL OF DRUG

Agonizingly, the first clue was in plain sight a year ago, but researchers at the National Institutes of Health didn't know enough about how the drug worked to recognize what it meant, the study's lead scientist says.

"Something terrible happened and we missed it," Dr. Jay Hoofnagle said in an emotional interview describing the horror of realizing the drug was killing people months after they stopped taking it.

"The dreadful thing [is] waiting to see what will happen," he said, his voice trembling, before learning of the most recent death. "I just hope we're over the worst."

The drug Fialuridine, or FIAU, had shown great promise for fighting the hepatitis B virus, which can cause deadly cirrhosis and liver cancer. When dogs passed toxicity tests unharmed, the Food and Drug Administration approved FIAU for human trials.

Too late, scientists discovered that in humans, FIAU stealthily attacks the very building blocks of cells in livers, kidneys and nerves.

Five people treated with FIAU have died of liver and kidney failure, despite liver transplants for three of them.

On Tuesday, a 37-year-old woman succumbed after two months in critical condition and two liver transplants at the University of Virginia Medical Center. One volunteer remains in serious condition there, and another is recovering from an Aug. 4 transplant at Emory University Hospital in Atlanta.

Additionally, Hoofnagle fears other antiviral drugs such as the AIDS drugs AZT and ddI, which are known to be toxic, may attack patients the way FIAU did. The first clue that FIAU was dangerous came in August 1992, when a man who had taken FIAU developed painful nerve damage. Paul Melstrom of Phoenix and 23 other volunteers participated in a 28-day NIH study of FIAU, from mid-April to mid-May last year. Almost four months later, Melstrom, 53, contracted severe neuropathy in his feet and legs. Another patient had minor neuropathy.

"It was so obvious to me it was the FIAU," Melstrom said from Arizona. "There's nothing about my life that changed in 1992, but there was one hallmark event. That was the taking of the FIAU."

But the NIH couldn't prove FIAU was to blame. Many things cause neuropathy, including alcohol. Melstrom is a recovering alcoholic and once had a bout with mild neuropathy.

So the agency continued the trial this spring, giving the drug to 15 otherwise healthy hepatitis patients for up to 11 weeks.

Keywords:
FATALITY