REDUX:  Unheeded Warnings on Lethal Diet Pill

Wednesday, December 20, 2000 |  Print this
 Heart damage causes billions of dollars in potential legal liability.

By DAVID WILLMAN, Times Staff Writer

Dr. Leo Lutwak was the lead FDA medical officer reviewing the diet drug
Redux, which in one pill approximated half of the slimming cocktail known as
fen-phen. He said he resisted its approval.
BRIAN WALSKI / Los Angeles Times

     Before coming to the FDA as a medical officer in 1989, Dr. Leo Lutwak
had specialized in the fields of obesity and osteoporosis as a Cornell
University professor, as a drug company consultant and as a practicing
physician. He said he hired on at the FDA because he relished the scientific
challenge of new drugs and the call of public service.
     In 1995, Lutwak was the lead FDA medical officer reviewing the diet
drug Redux, which in one pill approximated half of the now-infamous slimming
cocktail known as fen-phen.
     Both Lutwak and his boss, Dr. Solomon Sobel, told The Times that they
resisted the approval of Redux.
     "I, as the primary reviewer, felt that the drug had low effectiveness
and very high risk for neurotoxicity and pulmonary hypertension," a disorder
that damages the respiratory system, Lutwak said.
     "I was insisting on a black box," he added, referring to the bold
border at the top of a prescription label that alerts doctors and patients
to severe life-threatening risk. "But the management accepted the company's
arguments against the black box. And I don't know why."
     Sobel, director of the FDA's endocrine and metabolic drugs division
throughout the 1990s and who remains at the agency, was concerned that Redux
did not work. He said he refused to sign the agency's formal letter of
     "Well let me tell you," Sobel said. "I was supposed to sign off on that
letter. . . . I told [an FDA administrator, Dr. James] Bilstad that I would
not sign on it. If he wanted to approve it, he should sign on it. And the
record shows, he's the one who signed on it."
     How Redux came to be approved in April 1996 remains a curiosity.
     After an FDA advisory committee voted, 5 to 3, that evidence of Redux's
safety was "not sufficient to warrant approval," Bilstad took the unusual
step of scheduling a second meeting, just two months later. At that meeting,
in November 1995, the committee voted, 6 to 5, to recommend approval.
     Lutwak said he was "shocked" by the scheduling of the second meeting.
     Much was riding on Redux. Analysts at one securities firm, Rodman &
Renshaw, estimated the drug would gross $1.8 billion within four years.
     But Redux was withdrawn on Sept. 15, 1997, after heart valve damage was
detected in patients put on the drug. Civil lawsuits that are now pending
also allege that Redux caused the potentially fatal respiratory disorder
that had worried Lutwak.
     American Home Products Corp., which marketed Redux and Pondimin, a diet
pill that was used widely in formulations of fen-phen, agreed last fall to
pay or set aside $4.75 billion to settle lawsuits related to the drugs'
potential to cause heart valve damage. The company more recently has set
aside up to an additional $4.75 billion to pay other patients who have
suffered from the respiratory condition or heart valve damage.
     "We are aggressively settling as many cases as we can," said Douglas
Petkus, a spokesman for Wyeth-Ayerst Laboratories Inc., a subsidiary of
American Home.
     In its one year on the market, Redux generated sales of $255.3 million.
The FDA received reports before and after the withdrawal that cited Redux as
a suspect in 123 deaths.
     Bilstad, who left the FDA in January, declined to be interviewed this
fall when reached at his home.
     In a written statement, Woodcock acknowledged that "the possibility of
including a black box warning" on Redux's label was discussed with
Wyeth-Ayerst. But, she said, FDA officials decided "it was not warranted."
She said that the drug's potential respiratory risk was noted within the
labeling in bold type. Before Redux went on the market, Woodcock said,
"there was no hint" that it would cause heart valve damage.
     Lutwak, now 72, said he regrets the approval of Redux--and the agency's
failure to insist on a black box warning.
     "It might have saved lives," he said.