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SUNDAY REPORT

Hidden Risks, Lethal Truths

Warner-Lambert won approval for Rezulin after masking the scope of liver injuries in clinical studies

June 30, 2002|DAVID WILLMAN | TIMES STAFF WRITER

WASHINGTON — Newly obtained internal documents show that Warner-Lambert Co. executives who promoted the diabetes pill Rezulin masked from federal regulators early indications of the drug's danger to the liver and later delayed sharing information about its lethal toxicity with family doctors.

The newly acquired materials show that company management rebuffed employees who questioned liver-injury totals from clinical studies that excluded 38% of the cases. At the time, Warner-Lambert was assuring doctors nationwide that the drug was as safe as a placebo, the harmless pill used as a control in medical testing.

The story of the Food and Drug Administration's handling of Rezulin is well known. After the agency gave the drug "fast-track" approval in early 1997, scores of liver-related deaths were linked to the pill. Rezulin was withdrawn from the U.S. market in March 2000. By then, it had generated $2.1 billion in sales for Warner-Lambert.

But only now is a picture emerging of Warner-Lambert's actions, showing how a major drug maker can obscure risks and then win blockbuster sales. Pfizer Inc., which acquired Warner-Lambert in mid-2000, has turned over voluminous documents to plaintiffs' lawyers in response to more than 2,000 lawsuits filed on behalf of approximately 5,100 Rezulin users or their survivors. Many of the materials have been kept out of public view by judges' orders. The Times obtained copies of the materials, along with transcripts of recent sworn statements by company executives and others.

One of the central figures in the documents is Dr. Randall W. Whitcomb, Warner-Lambert's vice president for diabetes research. Without telling the FDA, Whitcomb used an unorthodox method to count the number of liver injuries among patients who used Rezulin while using different criteria to count liver injuries among patients taking a placebo. The result trimmed the number of cases the company reported to the regulators and to doctors nationwide, giving a more benign view of the drug's risks.

Pfizer said in a recent financial statement that a federal grand jury based in Greenbelt, Md., has sought documents and the sworn testimony of certain former Warner-Lambert employees regarding Rezulin.

"We are cooperating with this investigation," Pfizer said in the financial report, filed March 28 with the Securities and Exchange Commission. The investigation is being led by the U.S. attorney's office in Greenbelt and by agents from the FDA's Office of Criminal Investigations.

It is a crime in the U.S. to deliberately conceal an important fact about the safety of a prescription drug.

A spokesman for Pfizer, Robert J. Fauteux, said in a written statement that his company "believes that, in developing Rezulin, Warner-Lambert made a valuable contribution to the effort to control diabetes." Fauteux also said that, in Pfizer's view, the product labeling for Rezulin and other warnings, approved by the FDA, "appropriately communicated the risks associated with the medication, including the risk of liver injury."

Rezulin, he said, "offered an innovative treatment option to nearly 2 million patients." Citing the pending civil lawsuits, Fauteux declined to respond to specific questions posed by The Times.

The newly obtained materials also reveal that:

* Company representatives discussed in 1998 how best to persuade doctors treating Latinos "to take the risk of prescribing Rezulin." The same internal company document described the Latino patients as "easy to intimidate."

* When an Arcadia woman, Rosa Delia Valenzuela, suffered liver failure and died in December 1998 while taking the drug in a Warner-Lambert study, company representatives argued against promptly alerting the hundreds of doctors nationwide who continued to conduct the research on more than 2,000 other patients.

* As the deaths of U.S. patients mounted, Warner-Lambert offered to--and did--reimburse doctors if they got sued for prescribing Rezulin. The American Medical Assn. has warned doctors against such reimbursements, terming them "unacceptable gifts."

The FDA now attributes 94 liver failures, 66 of them fatal, to Rezulin. A review by The Times of reports filed with the FDA found that Rezulin was cited by doctors and others as a suspect in 556 deaths, including but not limited to the liver failures. Because reactions to prescription drugs are reported voluntarily in the U.S., epidemiologists suspect that as few as 1% to 10% of the actual events are made known to the FDA.

The hospitalizations and deaths stand in contrast to the benefits offered by Rezulin. The drug lowered blood-sugar levels but was not proved to offer any benefits that would either save a patient's life or reduce the serious complications of adult-onset diabetes, including stroke, amputation or blindness.

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