3 Lawmakers Question FDA on Diabetes Pill Approval

Saying that the issues “go to the heart of the public’s confidence” in the Food and Drug Administration, three senior House Democrats are seeking answers to extensive questions about the agency’s approval of the diabetes pill Rezulin.

In a four-page letter to Dr. Jane E. Henney, the newly installed FDA commissioner, Reps. John D. Dingell of Michigan, Sherrod Brown of Ohio and Henry A. Waxman of Los Angeles said that the agency’s handling of the drug calls into question whether the public is being adequately protected.

The congressmen asked Henney to catalog the extent and dates of at least 33 Rezulin-related deaths and other “cases of serious liver damage.” They also asked Henney why Dr. John L. Gueriguian, the FDA medical officer assigned to evaluate the safety of Rezulin, was stripped of his assignment after raising safety concerns and recommending that the agency reject the drug.

The congressmen told Henney that their inquiries were prompted by disclosures in a Los Angeles Times series, published Dec. 6 and 7. The articles revealed that senior FDA officials dismissed explicit warnings of danger while racing to approve Rezulin and that the government’s top diabetes researcher entered a consulting deal with the manufacturer of the drug while overseeing its inclusion in a $150-million federal study.

In their letter to Henney, the three congressmen posed questions that focus squarely on the FDA’s basis for keeping Rezulin on the market, despite liver-failure deaths that have mounted since regular monitoring of patients was recommended 13 months ago.

“In light of the rising number of patient deaths and cases of liver damage, does the agency continue to believe that testing of liver function is an adequate means of preventing future fatalities and serious adverse reactions?” the congressmen asked.

The letter, received by Henney on Tuesday, also asked: “What proportion of patients are complying with the liver function tests?”

To date, FDA officials and representatives of Warner-Lambert Co., the maker of the drug, have said in interviews that Rezulin is safe for the more than 1 million reported users when taken with liver-function monitoring. They also have acknowledged that they do not know how many patients are submitting to the tests. Other experts say that, based on anecdotal observations, compliance with the liver testing appears inconsistent.

Rezulin has been associated with the liver-failure deaths of at least 33 people in its first 21 months on the market in the United States and Japan. The pill is prescribed to patients with adult-onset diabetes to help lower their blood sugar.

A spokesman for Henney, who was nominated by President Clinton in June, said that the FDA will respond to the letter “in an appropriate manner.”

Last week, members of an FDA advisory committee told The Times that they would have recommended liver testing for Rezulin patients before the drug went on the market in March 1997--if the agency had alerted them to occurrences of potentially life-threatening liver toxicity detected in research patients who were taken off the drug.

It was not until November 1997--eight months after Rezulin went on the market--that the FDA and Warner-Lambert recommended that patients undergo regular liver-function testing. That recommendation came after the first reported liver-failure death of a Rezulin patient.

The congressmen, in their letter to Henney, posed 15 questions and requested a variety of transcripts, reports, internal e-mail correspondence and other documentation. This includes FDA records on Rezulin’s “potential risks of cardiovascular or liver damage.”

The congressmen also asked Henney to answer whether Dr. Richard C. Eastman of the National Institutes of Health, the federal government’s top diabetes researcher, had “any communications” with FDA staff “regarding the approval of Rezulin.”

The Times’ series disclosed that Eastman entered into a formal consulting arrangement with Warner-Lambert in November 1995--at the same time he was overseeing the $150-million federal study. Eastman and his colleagues selected Rezulin for use in the nationwide “Diabetes Prevention Program” in mid-1996--before the FDA approved the drug for general use.

Rezulin was withdrawn from the NIH study six months ago, after the liver failure and death of a 55-year-old high school teacher from East St. Louis, Ill.

Saying that “these issues . . . go to the heart of the public’s confidence in the FDA,” the congressmen concluded in their letter to Henney:

“We hope you agree that it is in the [FDA’s] and the public’s best interests that any doubts concerning the rigor and objectivity of the agency’s approval of new drugs be addressed swiftly and conclusively.”

Times on the Web: A series of stories on the diabetes drug Rezulin and the deaths related to its use is available on The Times’ Web site: https://www.latimes.com/rezulin