REZULIN: FDA Advisory Panel Extends Cautious Approval
Citing concerns about potential liver damage linked with the diabetes drug Rezulin, an FDA advisory panel called for tighter restrictions on the drug's use but stopped short of recommending that Warner-Lambert Co.'s blockbuster drug be pulled from the market. The 12-member advisory panel concluded unanimously Friday that "Rezulin's benefits outweighed its risks when used with other anti-diabetes drugs." In a second vote of 11-1, the panel said that the drug's benefits outweighed its risks when used in combination with insulin. On an 8-4 vote, the advisors urged the FDA to withdraw approval for Rezulin as a stand-alone treatment and recommended that the drug be used only after other treatments have failed (Schwartz, Washington Post, 3/27). But even with the restrictions, the New York Times reports, "some panel members seemed uneasy" about giving Warner-Lambert the green light. "I'm very uncomfortable about it," said panelist Dr. Jules Hirsch of Rockefeller University, "I think some of these people are going to get liver failure" (Stolberg, New York Times, 3/27). If Rezulin continues to be widely prescribed, he said, "in five years there will either be hundreds of people who will die of liver disease or thousands."
Head to Head on Risks
The "tense, day-long meeting overflowing with securities analysts, reporters and drug industry scientists" pitted FDA epidemiologist David Graham against Warner-Lambert executives, the Wall Street Journal reports (Langreth/Sharpe, 3/29). According to Graham, the FDA has verified Rezulin's role in 43 cases of liver failure, 28 of which lead to patient death (Willman, Los Angeles Times, 3/27). But Graham argued that the 43 cases likely represent only a fraction of the deaths attributable to Rezulin, adding that the drug may have caused up to 400 deaths. Further, the length of time patients spend on Rezulin compounds liver toxicity, Graham said, predicting that one in 1,800 patients on Rezulin for six months would develop acute liver failure. Graham's figure stands in contrast to the one in 45,000 estimate offered by Dr. Robert Zerbe, the company's senior vice president of clinical research. Zerbe noted that "[t]housands of people have used Rezulin for six months to a year," and if the risks were as high as Graham contends, there would be "an epidemic of liver failure." Graham conceded that he knew "of no patient who died after taking Rezulin for a year" (Neergaard, AP/Contra Costa Times, 3/27). Openly frustrated with conflicting data on toxicity monitoring, Rockefeller University's Hirsch said, "We are seriously in need of new information. I have almost never had a meeting here that so confounded me" (New York Times, 3/27). The Wall Street Journal noted that sales of Rezulin would be "sharply curtailed" if the FDA adopts the advisory panel's recommendations (3/29).