[British Medical Journal article below]
LOS ANGELES
-- Warner-Lambert Co. downplayed liver damage concerns as it sought
federal approval for its diabetes drug Rezulin, the Los Angeles Times reported
Sunday.
Warner-Lambert assured the U.S. Food and Drug
Administration that the drug's risk was low, while FDA officials gave the
company inside information and favors at key points in the drug's development,
the newspaper reported, citing previously unpublicized company and government
documents.
The company knew at least 12 people had suffered
potentially life-threatening liver damage during clinical trials.
In December 1996, Warner-Lambert's vice president
for diabetes research, Dr. Randall W. Whitcomb, told the Endocrine and Metabolic
Drugs Advisory Committee of the FDA that incidences of damage were
"comparable to placebo" in the studies, the Times said.
In fact, 2.2 percent of the patients who took the
drug had suffered liver problems, compared to 0.6 percent who took the
ineffective placebo pills.
"I don't think that these numbers are, are
all that different," Whitcomb said in a recent deposition for several
lawsuits brought against the company.
The FDA approved the drug in January 1997. It
garnered $2.1 billion in sales before it was withdrawn last spring after being
suspected of causing 391 deaths, including dozens involving liver damage.
A message left at New York-based Pfizer Inc.,
which acquired Warner-Lambert last year, was not immediately returned.
FDA spokesman Lawrence Backorik said Sunday that
he was "not in a position to comment on allegations concerning the conduct
of the company or former FDA employees that were involved in the review of
troglitizone."
Troglitizone is the generic name for Rezulin.
"The FDA bases its actions on science."
Backorik said. "When, in our view, the risk of approved products outweighs
the benefits, FDA sees that the product is withdrawn."
The Times, citing Warner-Lambert e-mails and
memos, said the company knew as early as 1993 of at least one case of a patient
who showed liver damage after taking Rezulin.
Last year, a consultant to Warner-Lambert who
helped conduct two of its studies alleged that the firm "deliberately
omitted reports of liver toxicity and misrepresented serious adverse events
experienced by patients in their clinical studies."
The remarks by Dr. Janet B. McGill, a St. Louis
endocrinologist, were made in a letter to Sen. Edward Kennedy, D-Mass.
Dr. John Gueriguian, an FDA medical officer
assigned to examine Rezulin, told the company as early as 1994 that he was
concerned about "potential toxicities." But Gueriguian's boss, Dr. G.
Alexander Fleming, told a Warner-Lambert executive in 1995 that "he would
ease Dr. Gueriguian out" if the executive was displeased with him,
according to a memorandum from the executive.
Gueriguian was removed from the case in 1996.
Fleming e-mailed a copy of Gueriguian's unflattering medical review to the
company, but it was withheld from the advisory committee that examined the drug,
the newspaper said.
Two days before the advisory committee meeting,
Fleming e-mailed Warner-Lambert's executive vice president for regulatory
affairs, Irwin G. Martin, saying "the drug looks like it ought to be on the
market. Loosen up and put on a good presentation. Call if you need help."
The Times said the company also received
behind-the-scenes help from Dr. Murray M. "Mac" Lumpkin, who now is
being considered for appointment as FDA commissioner, and Dr. Henry G. Bone III
of Detroit, chairman of the advisory committee.
Pfizer Inc. said last fall that it was defending
against 383 Rezulin-related lawsuits in federal and state courts.
Warner-Lambert played down the potentially fatal risks associated with troglitazone during the approval process and received help from federal drug regulators in pushing the drug towards marketing approval, an article published in the Los Angeles Times has claimed.
The newspaper based its report on company and government documents, some secretly obtained, as well as email communications, which showed that officials from Warner-Lambert had collaborated closely with certain senior officials in the US Food and Drug Administration (FDA) during the approval process and later, when the company was being pressured to take the drug off the market.
The FDA initially approved troglitazone, marketed as Rezulin, in January 1997 for treatment of type 2 diabetes. The drug was pulled from the market in March 2000 because of the number of reports of liver failure associated with its use. At an FDA advisory committee meeting last year, regulators reported that there had been 90 cases of liver failure among patients taking the drug since its launch.
As portrayed in the records, FDA officials provided Warner-Lambert with inside information and favours at critical moments throughout the development and marketing of troglitazone, according to the Los Angeles Times. At least one senior manager believed that if an FDA medical officer who had questioned the drug's safety and effectiveness did not please the company, he would be "out." Soon enough, he was, prompting another executive to report internally that a "hurdle" had been cleared for troglitazone.
In addition, executives knew that patients who took the drug in clinical studies had developed life threatening liver damage, yet the company assured an FDA panel that the risk was trivial. The company's assurances helped to win swift approval for troglitazone four years ago from the FDA. The newspaper, citing Warner-Lambert's emails and memorandums, said that the company knew as early as 1993 of at least one case of a patient who showed liver damage after taking troglitazone.
Dr John Gueriguian, an FDA medical officer assigned to examine troglitazone, told the company as early as 1994 that he was concerned about "potential toxicities." But Dr Gueriguian's boss, Dr G Alexander Fleming, told a Warner-Lambert executive in 1995 that he would "ease Dr Gueriguian out" if the executive was displeased with him, according to a memorandum from the executive.
Dr Gueriguian was removed from the case in 1996. Dr Fleming emailed a copy of Dr Gueriguian's unflattering medical review to the company, but it was withheld from the advisory committee that examined the drug, the newspaper said.
Two days before the advisory committee meeting, Dr Fleming emailed Warner-Lambert's executive vice president for regulatory affairs, Irwin Martin, saying, "the drug looks like it ought to be on the market. Loosen up and put on a good presentation. Call if you need help."
Pfizer, which purchased Warner-Lambert last year, now faces almost 400 lawsuits related to troglitazone. In a statement issued on Monday afternoon, Pfizer said that it "strongly disagrees" with the characterisation by the Los Angeles Times of Warner-Lambert's behaviour.
"While it does not comment in detail on matters related to current litigation, Pfizer affirmed today that Warner-Lambert appropriately disclosed the risk of adverse liver events before Rezulin . . . was commercially marketed," the statement reads.
FDA spokesman Lawrence Backorik said that he was "not in a position to comment on allegations concerning the conduct of the company or former FDA employees who were involved in the review of troglitazone."
"The FDA bases its actions on science," Mr Backorik said.
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