2 New FDA Panelists Have Ties to Rezulin Maker
On the eve of a crucial hearing to reassess the diabetes pill Rezulin, the Food and Drug Administration has appointed two new members to an advisory panel--both of whom have financial ties to the drug’s manufacturer.
The newly installed committee members--Dr. Mayer B. Davidson of the UCLA School of Medicine and Dr. Saul M. Genuth of Cleveland--have received income during the last two years as leaders of a private diabetes education group funded exclusively by the makers of Rezulin, the Warner-Lambert Co. and its Japanese partner.
The leaders have received about $8,500 a year in fees from the company-funded group, government records indicate. The group has encouraged doctors to aggressively treat adult-onset diabetes, often with Rezulin.
On Friday, the FDA panel is expected to recommend whether to restrict, withdraw or expand use of the drug, which has been linked to dozens of liver-failure deaths. This same committee in late 1996 unanimously endorsed Rezulin, which has registered sales in excess of $1 billion.
It was announced this week that the Medicines Control Agency, the FDA’s British counterpart, has refused to allow reintroduction of Rezulin in the United Kingdom. The British agency determined that the risks of Rezulin outweigh its benefits.
The FDA’s eleventh-hour appointments were made by the office of Commissioner Jane E. Henney without public notice. This is not the only instance of a relationship between the company marketing Rezulin and government agencies that oversee the testing and safety of the drug.
NIH Researcher Was Paid $78,455
The government’s top diabetes researcher at the National Institutes of Health is under investigation for accepting $78,455 in total compensation from Warner-Lambert and its affiliates.
One of the new FDA appointees said his financial tie to the Warner-Lambert affiliate was known to the agency.
“I gave all this information to the FDA so I have to leave it up to them as to whether they felt there would be any conflict of interest,” Davidson said.
FDA officials said the appointments were made to add further expertise to the Endocrinologic and Metabolic Drugs Advisory Committee. The additions increased the panel’s voting members from 11 to 13. Although the recommendations made by the FDA panel are not binding, the agency usually follows them.
Legally, the FDA can disregard conflicts of interest among advisory committee members if officials believe that the conflict is outweighed by the expertise to be gained. Even when a potential conflict of interest is acknowledged, the advisory committee member is either granted a “waiver” allowing participation or disqualified. In any case, the underlying details are not publicly revealed.
The FDA’s decision to reassess Rezulin follows a Times series, published on Dec. 6 and 7, disclosing how the FDA raced to grant “fast track” approval to the drug in early 1997 while dismissing explicit warnings of potential danger. Last week The Times disclosed that doctors and others had reported the deaths of 155 patients in which Rezulin was cited as a “suspect” drug. About 60% of those cases involved findings of liver damage.
Warner-Lambert officials said Rezulin is effective and safe, when used in concert with regular liver-function tests. They have said they will ask the advisory panel to support expanded use of the drug.
Kathleen R. Reedy, executive secretary of the FDA advisory committee, said the appointments of Davidson and Genuth were made with the consent of senior agency officials.
Davidson and Genuth are among 12 diabetes specialists who have served over the last two years as “faculty” members of the National Diabetes Education Initiative. Since its inception in 1996, the group has been exclusively financed by grant money from Warner-Lambert Co. and a joint venture that the company formed with Sankyo, a Japanese firm that developed Rezulin.
Neither the appointees nor an official of the Diabetes Initiative would say how much money is paid to the group’s faculty.
Another long-standing faculty member of the Diabetes Initiative--Dr. Richard C. Eastman, the federal government’s top diabetes researcher--resigned from the group in December after The Times disclosed that Eastman had accepted $78,455 in total compensation from Warner-Lambert and its affiliates between November 1995 and December 1997, government records show.
NIH Director Harold E. Varmus has strongly questioned Eastman’s acceptance of income from Warner-Lambert and other pharmaceutical firms. The matter is now under investigation by the inspector general of the Department of Health and Human Services.
Eastman has said he acted with the consent of his immediate supervisor.
No ‘Cause for Alarm,’ New Panelist Says
FDA officials said they are prohibited from providing information about the sources of income or potential conflicts of interest of any of the advisory committee members who are to meet Friday.
Genuth said in an interview last fall that he considered Rezulin appropriate for some patients. He also has served as chairman of a separate committee that advised NIH leaders to remove Rezulin from a nationwide diabetes-prevention experiment last June, after a participant taking the drug suffered sudden liver failure and died. He declined on Wednesday to discuss his FDA appointment.
Davidson, a past president of the American Diabetes Assn., was widely quoted vouching for the drug’s safety when Rezulin was withdrawn from the market in Britain in December 1997.
“I personally don’t think it is cause for alarm,” Davidson told the Philadelphia Inquirer at the time. “It’s been known since the clinical studies that 2% of [Rezulin] patients had these increases in liver enzymes. Once you stop the drug, it is reversible.”
Yet, medical records for some Rezulin patients who died show that their liver damage continued even after they had stopped taking the pills.
The FDA recently has acknowledged the liver-related deaths of 100 Rezulin patients and identified 33 of those fatalities as “associated” with the drug. The agency has not explained its basis for excluding the remaining 67 liver-related deaths.
At Friday’s meeting, FDA staff is expected to analyze whether the recommended liver-function tests are adequately protecting Rezulin patients. The advisory committee also may be asked to assess whether Rezulin is safe enough to continue being used as a stand-alone diabetes pill.
Rezulin is one of 10 or more drugs available to treat adult-onset, “Type 2” diabetes, a condition characterized by elevated blood-sugar levels. Patients with juvenile-onset, “Type 1” diabetes must take daily injections of insulin to survive.
The advisory panel members who voted on Dec. 11, 1996, to endorse Rezulin--five of whom are scheduled to attend this Friday’s session--were provided scant information about Rezulin’s liver toxicity. They were not informed that the veteran FDA medical officer assigned to examine Rezulin, Dr. John L. Gueriguian, had recommended that the drug be rejected, in part because of his concern about liver toxicity.
At Friday’s meeting, Warner-Lambert will be allotted 90 minutes to make its case before the advisory panel. FDA staff will be given one hour. An opponent of the drug, Dr. Sidney M. Wolfe of Public Citizen, the Ralph Nader group, will be permitted to speak for 10 minutes, as will a representative of the American Diabetes Assn.
Warner-Lambert has contributed at least $500,000 annually to the ADA during the past two years, according to the organization’s Internet site.
Still, the incoming president of the ADA, Dr. Bruce Zimmerman of the Mayo Clinic, is not a promoter of Rezulin.
“Personally, as a physician who treats patients . . . I think the medication has been overused and over-promoted, for what it is,” Zimmerman said in an interview, adding:
“We continue to see, on a weekly basis, patients who are on the medication and, at least in my medical judgment, had no reason to be on it, because there were alternative medications that are cheaper and potentially safer that had not been tried.”
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Researcher Janet Lundblad contributed to this story.
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A series of Times stories on the FDA approval of Rezulin and deaths related to its use is on The Times’ Web site: https://www.latimes.com/rezulin
