MEDICAL OFFICER REMOVED AFTER OPPOSING DRUG'S APPROVAL

LOS ANGELES -- A veteran medical officer who opposed approval of a
popular diabetes drug was removed as its chief reviewer by the Food
and Drug Administration, the Los Angeles Times reported Sunday.

Two other FDA officials who recommended approving the drug, Rezulin,
conceded the agency initially overlooked compelling evidence of its
danger to the liver, the newspaper said.

Rezulin is used to treat adult-onset diabetes and is used by more than
1 million people. The drug has been linked to at least 26 deaths worldwide.

The FDA approved Rezulin in December 1996 to become the most quickly
endorsed diabetes pill in the agency's 60-year history. Because
Rezulin was the first in a new class of diabetes drugs, the FDA gave
it a special ``fast-track'' review, taking six months to make the
decision -- less than half the normal approval time.

In October 1997, it issued the first warning about liver
toxicity.

Britain withdrew the drug following the first reported deaths. The FDA
said Rezulin remains on the U.S. market because it is the only
diabetes drug that resensitizes the body to insulin -- a hormone that
converts blood sugar into energy. Rezulin helps lower blood sugar
enough that many patients report needing fewer daily injections of
insulin.

The FDA recommends that Rezulin patients have regular blood testing in
hopes of detecting early liver damage before it becomes
life-threatening.

``We have been evaluating this drug very carefully since we became
aware that liver disease was a significant problem,'' said Dr. James
M. Bilstad, the senior FDA official who gave final approval to
Rezulin. ``We have in the past and continue up to this time to
conclude that we still believe the benefits outweigh the risks.''

Dr. John L. Gueriguian, a veteran FDA medical officer assigned to
evaluate Rezulin, recommended rejecting the drug after documenting its
possible danger to the liver. Senior FDA officials removed him from
the review in the late fall of 1996, according to Gueriguian and an
agency memo.

Gueriguian, now a drug industry consultant, said he stands by his
review. ``If (Rezulin) hadn't have been approved, at least 21 people
would be alive now. In all probability, many more than that,'' he said.

Two other doctors, Robert I. Misbin and G. Alexander Fleming, warned
the 46DA about possible serious side effects. Fleming said he
suggested restricting the recommended use of Rezulin but relented
following resistance from Warner-Lambert Co., the drug's
manufacturer.

``I said to myself, `At this very moment as I am writing this, there
are 2,000 patients that are going to die of this drug, unless we do
something,''' Misbin told the Times.

``We believe this drug brings a unique and significant benefit for
patients,'' said Dr. Randall W. Whitcomb, Warner Lambert's vice
president for diabetes research. ``And while it has a risk, (this) is
true of all medications.''

Gueriguian and the company said they had one meeting in which the
doctor voiced doubts about Rezulin in intemperate language. After the
company complained, the FDA removed Gueriguian from reviews of Rezulin
and any other Warner-Lambert drug, the Times said. Warner-Lambert said
it objected to Gueriguian's inappropriate comments, not his concerns
about Rezulin.

Checked-by: Patrick Henry