FDA ‘Collaborated’ with Warner-Lambert on Rezulin, the LA Times Reports
Newly-obtained memos and emails reveal that senior FDA officials "quietly collaborated" with drug company Warner-Lambert in securing approval for the "now-discredited" diabetes drug Rezulin, the Los Angeles Times reports. Rezulin gained "swift approval" from the FDA in 1997, but was pulled from the market last March after being cited as the cause of 391 deaths, 63 of which resulted from liver failure. New information shows that although Warner-Lambert was aware that patients in clinical trials for Rezulin had suffered potentially fatal liver damage, the company "assured" the FDA that the risk was "trivial." Meanwhile, FDA officials "collaborated closely" with Warner-Lambert to gain approval for the drug, providing the company with "inside information and favors at critical moments throughout the development and marketing of Rezulin." Last November, the FDA released an internal report acknowledging that the agency committed "possible missteps" in its handling of Rezulin, and called for a "re-evaluat[ion]" of its policies on prescription drug regulation.
The Times investigation found that in 1996, Warner-Lambert was "concern[ed]" about Rezulin's link to liver toxicity and had prepared a label recommending that patients taking the drug should be examined by doctors after three months, and then monitored every six months. But the company "abandoned" this recommendation before seeking approval from the FDA's Endocrine and Metabolic Drugs Advisory Committee in December 1996. In subsequent meetings with the committee, Warner-Lambert officials downplayed the incidence of liver injury among patients in clinical trials.
Dr. Randall Whitcomb, Warner-Lambert's vice president for diabetes research at the time, told an FDA advisory committee on Dec. 11, 1996, that occurrences of liver injury in trial patients were "comparable" to the levels of injury in patients taking placebos. However, incidence of liver injury was more than three times higher among patients taking Rezulin, the Times reports, with 2.2% of Rezulin patients experiencing liver damage, compared to 0.6% of placebo patients. In recent sworn deposition for lawsuits brought by plaintiffs in several states, Whitcomb said, "'Comparable' is ... an interesting word. Is 2.2% different than 0.6%? ... I think you could look at 2.2 and 0.6 and say that those are similar numbers, you know, when you look at this now. ... I don't think that these numbers are ... all that different." Warner-Lambert executives said that they did not see the need to recommend monitoring, as "no patient suffered liver failure in the original clinical studies."
But the Times reports that "at least 12" patients enrolled in clinical trials had suffered potentially life-threatening liver toxicity. Warner-Lambert publicly recommended liver monitoring for Rezulin patients in October 1997, but only after the first reported liver-failure deaths occurred. Only in March 1998 did Whitcomb publicly acknowledge the "severe liver-toxicity cases" observed during the clinical studies (Willman Los Angeles Times, 3/11).This is part of the California Healthline Daily Edition, a summary of health policy coverage from major news organizations. Sign up for an email subscription.