REZULIN: L.A. Times Reporter Recounts History

      Los Angeles Times reporter David Willman, who broke the story on the diabetes drug Rezulin, recounts the drug's history in a Sunday Times article, "The Rise and Fall of the Killer Drug Rezulin." Based on previously undisclosed documents and numerous interviews with government and private doctors over the past three years, the chronology details how Rezulin became "a touchstone for federal policymakers and for the doctors, patients and family members directly affected by the government's decisions." The Warner-Lambert drug generated excitement in 1996 as the first in a new class of medicines targeted at adult-onset diabetes and the first diabetes pill in history to be granted a six-month fast-track review by the FDA. But Willman reports that a "reconstruction of Rezulin's rise and fall shows that senior government officials repeatedly played down the drug's propensity to cause liver failure and death." In total, the FDA has confirmed 63 deaths and thousands of liver injuries attributed to Rezulin, although experts say the actual toll, including unreported deaths and adverse effects, could be as much as 10 times higher.

The Chronology
      When veteran FDA medical officer Dr. John Gueriguian found during his 1996 review of Rezulin that the drug provided "little significant therapeutic advantage" over existing diabetes treatment and was "unfit for approval" due to its potentially harmful side effects on the liver and heart, Dr. Murray Lumpkin, deputy director of the FDA's drug-evaluation center, acted on complaints from Warner-Lambert and removed him from the evaluation team, expunging his review from FDA files and cutting off his contact with the drugmaker. After ushering the new drug quickly through the approval process, Lumpkin, who also was responsible for managing the FDA's response to unexpected prescription drug-related deaths, repeatedly resisted the drug's withdrawal from U.S. markets, even after reports of patient deaths came in and the British government refused to allow Rezulin's reintroduction, citing safety concerns. Finally, after a Times report on the situation, newly appointed FDA Commissioner Jane Henney ordered a reevaluation of the drug in January 1999, but it took the actions of one group of rebel FDA medical specialists, known as "the Termites," to get the drug off the market. As Lumpkin continued to fight against the drug's withdrawal, creating "diversionary" tactics and other delays, the Termites pushed internally for Rezulin's removal. Then, Dr. Robert Misbin, a Termite who had supported Rezulin early on, took the cause to Congress, warning Rep. Henry Waxman (D-Calif.) and seven other lawmakers of the drug's fatal side effects and handing over "damning" research and internal emails regarding the FDA's handling of Rezulin. On March 15, Henney met with Lumpkin and his boss, Dr. Janet Woodcock, and within the next week, despite fears that withdrawal of Rezulin would further discredit the FDA's new fast-track approval system, officials released a statement that Warner-Lambert had agreed to remove the drug from the market. Woodcock said, "We are now confident that patients have safer alternatives" (6/4).