REZULIN: Will Its Failure Taint FDA, NIH?

      The troubled history of Warner Lambert's diabetes drug Rezulin sheds light on what some are characterizing as a collusion between industry and the government to bring new medications to the market more quickly. The Los Angeles Times reported yesterday that Dr. John Gueriguian, a senior Food and Drug Administration medical officer who opposed the drug's approval, had been removed as chief reviewer of the case. Moreover, the paper reports that "previously undisclosed cases acknowledged by FDA officials Friday show that ... precautions have not slowed the pace of patient deaths" from side effects associated with Rezulin. The new figures show that Rezulin caused sudden liver failure and death in 33 patients, up from the 21 deaths reported by the FDA in June, despite warnings to physicians that the drug caused liver problems in 2% of patients and an FDA recommendation that doctors monitor liver function carefully in patients taking the drug. The Times reports that the FDA removed Gueriguian after his recommendation that the drug be rejected because of its potential for liver damage sparked complaints from Warner Lambert officials. Another FDA doctor estimated that more than 12,000 Rezulin users would experience some liver injury and that 2,000 of them could die. While the FDA chose not to "reveal how many lives might be at stake," it did urge doctors to monitor liver function closely. The Times reports that Warner Lambert's resistance opposition also caused the FDA's Dr. Alexander Fleming to rescind a recommendation that Rezulin use be restricted (Willman, 12/6).

That's Not All
      A second article published in today's Los Angeles Times reports that the National Institutes of Health's top diabetes researcher supervised a $150 million federal study of Rezulin while working as a paid consultant for Warner Lambert. Dr. Richard Eastman, director of the division of diabetes, endocrinology and metabolic diseases at NIH's National Institute of Diabetes and Digestive Kidney Diseases, received thousands of dollars for serving on Warner Lambert's Rezulin National Speakers Bureau, which touted the drug's benefits to doctors. Eastman was quoted in a Warner Lambert press release as saying Rezulin "corrects the underlying cause of diabetes" -- a claim that federal regulators called "false and misleading." Eastman now denies having made the statement. The Times reports that "Eastman's senior rank and participation in [FDA] deliberations and decisions other than just the final votes to select Warner Lambert's drug calls into question" why Eastman's paid work for Warner Lambert was approved by FDA officials.

False Claims?
      The Times also reports that Warner Lambert made a series of false claims about Rezulin's safety and efficacy, despite possession of evidence to the contrary. Nonetheless, the company's stock prices have doubled since the drug was introduced, and Rezulin sales during the last 19 months top $965 million. The company claimed -- in full-page color advertisements in the New England Journal of Medicine -- that Rezulin had "Side Effects Comparable to Placebo," despite evidence from clinical trials that "Rezulin users were 3.6 times more likely to suffer liver injury than patients taking a placebo" (12/7).

Sudden Liver Failure
      The May death of a 55-year-old high school teacher whose adherence to "strict precautionary liver tests that FDA says should prevent such deaths" has further cast doubt "on the new era of accelerated approval" (Times, 12/6). Although Warner Lambert asserted that the woman's death was "unrelated to the study or the medication," the NIH, unable to dismiss the teacher's death so easily, was forced to decide whether to remove Rezulin from the "government's largest-ever study of diabetes" -- a "decision which fell in part to Eastman." Ultimately, NIH pulled the drug from the study June 4. Eastman said, "In the face of the case of liver failure -- and the inability to prevent that, even in the context of a very carefully controlled clinical trial -- the feeling was that it was not viable to continue." The Times reports that the "blend of public and business interests ... threatens to erode the trust that doctors and patients place in the government's top health officials" (Willman, 12/7).