Key FDA Aide in Rezulin Case Resigns

A senior Food and Drug Administration official who played a pivotal role in the agency’s controversial handling of the diabetes pill Rezulin has resigned his post and temporarily assumed a lesser position.

The resignation and reassignment of Dr. Murray M. “Mac” Lumpkin was announced in an internal e-mail last Friday by his boss, Dr. Janet Woodcock, director of the FDA’s drug review center. Woodcock told colleagues that Lumpkin had resigned “for personal reasons” after serving seven years as the center’s No. 2 leader.

She said Lumpkin would remain on the payroll for “the next several weeks . . . while he evaluates various options outside the center.” Lumpkin’s new position has no supervisory authority.

In her e-mail, Woodcock lauded Lumpkin for speeding the FDA’s reviews of newly proposed prescription drugs. “Mac has played a huge role in the center’s performance improvements,” she said.

It was in that central role, however, that Lumpkin backed the rapid approval of Rezulin--and then consistently opposed withdrawing the drug despite scores of reported liver failures and deaths.

After making Rezulin the nation’s fastest-approved diabetes pill, on Jan. 29, 1997, the FDA announced on March 21 of this year that the drug was being withdrawn because of safety considerations. The agency at the time attributed 91 reported liver failures, including 63 deaths, to Rezulin.

The circumstances surrounding the FDA’s handling of Rezulin are the subject of an investigation by the Greenbelt, Md., office of the U.S. attorney.

Lumpkin, 46, did not return calls seeking comment regarding his resignation. An FDA spokesman, Lawrence Bachorik, said he did not know the nature of Lumpkin’s personal considerations, as alluded to in Woodcock’s e-mail. Bachorik also said that he did not know whether the options being weighed by Lumpkin include a return to the pharmaceutical industry. Lumpkin had directed international research for Abbott Laboratories before coming to the FDA in 1989.

In late 1996 and early 1997, Lumpkin directed the FDA’s “fast-track” review and approval of Rezulin. The approval overrode the objections of Dr. John L. Gueriguian, a veteran agency medical officer, who warned of Rezulin’s potential to harm the liver and the heart.

After complaints from the manufacturer, Warner-Lambert Co., about Gueriguian’s use of intemperate language, Lumpkin in late 1996 directed that he be stripped of further involvement with Rezulin. According to physicians familiar with the matter, Lumpkin then took the unusual step of ordering that Gueriguian’s review be purged from FDA files.

On Dec. 1, 1997, Rezulin was banished from Britain after the first reported liver failures in the U.S. and Japan. Lumpkin, however, backed the desire of Warner-Lambert to keep the pill on the U.S. market. The FDA and Warner-Lambert announced that the labeling of Rezulin would be changed, advising patients to have their liver functions monitored monthly for the first six months after taking the pill.

This turned out to be the second of four safety-labeling changes for Rezulin within its first 27 months on the U.S. market. Each of the label changes recommended that patients have their liver functions checked more frequently, or for a longer period of time.

Both Lumpkin and Woodcock conceded later in interviews that they never had proof the monitoring would safeguard patients from sudden, drug-induced liver failure.

In early 1999, FDA epidemiologist Dr. David J. Graham warned that the liver monitoring was not protecting patients. Graham estimated that, as of that point, more than 400 Rezulin patients had suffered liver failure. He concluded that the blood-sugar-lowering pill--one of 10 then on the U.S. market--was among the most dangerous drugs in circulation.

Still, Lumpkin resisted FDA physicians’ efforts to seek the withdrawal of Rezulin.

Even at a final meeting of senior officials last March 21, when the decision was made to pull Rezulin from the market, Lumpkin argued for the drug.