Rezulin Wars

With the first handful of thousands of product liability suits nationwide just now coming to trial, the battle over the insulin-regulating drug Rezulin is just beginning — and as regional counsel for Pfizer Inc., Baltimore-based Goodell, DeVries, Leech and Dann is right there on the front lines.

Goodell, DeVries, Leech and Dann lawyers Charles P. Goodell Jr., left, and co-counsel Richard M. Barnes, say the jury verdict they won in Montgomery County Circuit Court last month shows that Warner-Lambert Co. appropriately handled the research, development and marketing of the controversial antidiabetes drug Rezulin.

Introduced in March 1997, Rezulin was hailed as a breakthrough in the treatment of adult-onset diabetes and a wonder drug, the first to be approved under the U.S. Food and Drug Administration’s fast-track protocol.Three years later — the day after the drug’s manufacturer withdrew it from the market amid claims that it caused liver damage — the filing of product liability suits began: some 2,000 to date, seven of which have come to trial, with mixed results, in the last four months.Maryland’s first taste of the litigation came in January, after one multi-million-dollar plaintiff’s verdict, three settlements after jury findings of liability, and one defense verdict. [See “Early Results,” below].After a month-long trial, a Montgomery County jury deliberated just one hour before finding Pfizer Inc., which had acquired manufacturer Warner-Lambert Inc. in June 2000, not liable for the plaintiff’s death.Goodell, DeVries’ lawyers Charles P. Goodell Jr. and Richard M. Barnes say their win shows the company handled the research, development and marketing of the drug appropriately, and that the scientific evidence does not support the plaintiffs’ claims. “We think the case was important,” Goodell said. “The jury not only had a full company case, but they also had a very complete analysis of hepatitis and liver disease in general, and what caused it in this specific patient. It was both a full-blown company case and a full-blown scientific case.”Goodell’s firm, which is on Pfizer’s national trial team as well as counsel for cases in Maryland, the District of Columbia, Virginia and West Virginia, convinced the jury that Rezulin was not liable in the death of Monica T. George, 67, a retired Rockville nurse.George died in September 1998 while awaiting a liver transplant, less than a year after she began taking Rezulin in November 1997 to treat Type II or “adult onset” diabetes — a disorder that occurs when the body stops metabolizing insulin from blood sugar.After a trial lasting almost a month, it took the Montgomery County jury just one hour of deliberation before deciding in favor of Pfizer, the world’s largest drug company.George’s lawsuit, filed by her three daughters, Elaine Shaw, Andrea Shaw and Donna Storey, is the sixth to be tried of more than 2,000 Rezulin cases pending in state and federal courts nationwide. Goodell said George’s case is a good example of the issues most juries will hear in these cases, particularly in how the company worked with the FDA within acceptable risks to develop a new class of drugs to help doctors “stack the deck” in the favor of people with already serious underlying chronic and progressive diseases.“I think what the jury saw was the FDA and the company working together to manage the issue. And I think they saw a situation where the company acted responsibly,” Goodell said.His co-counsel Barnes pointed out that George’s medical records showed her to be “insulin resistant” as far back as the late 1980s, and that a cardiologist who found “elevated blood sugar” suggested she be checked for diabetes when she was treated for coronary artery disease in the early 1990s.“Mrs. George was prescribed Rezulin in November 1997,” Barnes noted. “She was diagnosed in August 1998 with autoimmune hepatitis — acutely ill — and found also to have cirrhosis. I think the jury saw that blaming the drug just didn’t hold up in the face of all this evidence of chronic liver illness.“It was the chronic liver disease diagnosed in August 1998 that was going to take her life,” Barnes added.Pfizer spokesman Robert Fateaux agreed.“What’s important in Monica George’s case is that the plaintiffs said, and we said as well, ‘Let’s get the full information out in front of the jury.’ There was a full presentation of both sides, and the jury did have the opportunity to review the comprehensive medical, scientific, clinical and other related information quite fully.“And it was in light of that information the jury decided that Rezulin was an innovative drug that helped so many patients and that Warner-Lambert acted appropriately in developing, marketing and labeling it,” Fateaux said.Plaintiffs ‘hampered’But Chetna Gosain, one of two associates who works with Houston, Texas-based Zoe P. Littlepage, the Rezulin pioneer plaintiff’s lawyer who represented George, said the plaintiff’s trial team was hampered by “the confines of what the court would let in.”

Littlepage, who opened another Rezulin trial this week in Oklahoma, was not available for comment, Gosain said.“This is the most interesting case this firm has done, because the causation was so clear and the drug company itself stated that the drug was probably related to her death — as well as all the media attention it got due to the causation,” Gosain said.“Dr. Paul Watkins — Warner-Lambert’s own expert — said the liver-adverse events in Monica George’s case [were] probably related to Rezulin — the highest standard this company could attribute to causation,” she said.But Gosain said “defense counsel that got its every wish granted” and “inherently flawed jury instructions” resulted in the jury not really getting the whole picture.Chief among what the jury was not allowed to see was evidence of Warner-Lambert’s criminal convictions, which Gosain said had been admitted in a Missouri Rezulin case that settled in December. One such conviction was a November 1995 Warner-Lambert plea agreement to pay $10 million in fines after admitting that it fraudulently withheld information from the FDA about manufacturing problems with Dilantin and three other products.“If the company was convicted at a criminal level, that is something for a jury to be made aware of — and the tactics they regularly employ in the production and distribution of these drugs,” she said.“In the end, it’s the jury that decides. But if the jury doesn’t have everything to be presented to them, what do you do?” Gosain said.However, Pfizer spokesman Fateaux said it is important to keep focused on the key allegations of the case, which he said is what Montgomery County Circuit Judge Paul A. McGuckian did in the George case.“It’s important to focus on the actual issues before the court, because at times there is an attempt to try to bring all kinds of other things into evidence that really have little or no bearing on the central issues,” Fateaux said.Goodell said the George case was important to both parties to try on its own merits — not least due to the proximity of both the Bethesda-based National Institutes of Health and the FDA’s headquarters in Rockville.“It was an important case for them to try. It was an important case for us to try. The FDA’s right around the corner and the NIH is right down the street from the courthouse,” Goodell said.“It’s easy to make an allegation. It’s much harder to put an allegation in context. This jury seemed to understand that by taking bits and pieces of information out of context, the plaintiffs were trying to create new science in the courtroom,” he said.Pfizer’s position is that serious liver damage caused by Rezulin is “idiosyncratic” or “genetic” — unique and inherent to a particular patient’s conditions, Goodell said.“There is no risk-free therapy,” he said. “If you talk to diabetes-treaters, the risk of diabetes is so great that the risk of liver injury is a risk worth taking … . Hundreds of thousands of people nationwide are dying of diabetes and complications of diabetes over a relatively short period of time. The risk of Rezulin is minor in comparison to untreated diabetes.”According to Goodell, the plaintiffs maintained the drug “was a direct toxin that at a molecular level damaged the cells of every single person who took it. It was a hotly contested issue.”In the end, he said, the jury didn’t buy it. “Science isn’t created in the courtroom. Science is created in the research community. The ‘scientific evidence’ that they wanted the jury to accept was not created in the scientific community,” Goodell said.To Goodell and his client, Rezulin is not inherently unsafe, but in time became an “outmoded therapy” which gave way to a safer alternative. “Hopefully, it’s the progress of science as things become available,” he said. “Rezulin was handled appropriately.” Underlying causeHowever, another plaintiff’s lawyer disagreed.Robert K. Jenner represents Rosetta M. Seay, the mother of Adrian C. Seay, who died at Washington Hospital Center in Washington, D.C., in March 1999 at the age of 37 from irreversible liver damage after being treated with Rezulin. “With all due respect to my colleague Charlie Goodell, to say that this verdict sends a message that the company acted responsibly is just — inaccurate,” Jenner said. “The special verdict sheet in the Montgomery County case had one question and one question only: Did Rezulin cause the lady’s death? They said ‘no’ and went home.”The Montgomery County verdict will have no bearing on what he believes he will be able prove when he tries his case in Superior Court in D.C., Jenner said. The Seays seek $30 million in compensatory and punitive damages. Goodell, who represents Pfizer in that case as well, said he expected the case to go to trial this November.“In terms of any precedential impact that verdict may have on future cases, the answer is ‘zero’,” he added. “They didn’t even get to the questions: Did the company act responsibly? Did the company hide things from the FDA? Did the company hide things from doctors?“They didn’t even get to that because the lady had an underlying condition that caused her death,” Jenner said. Jenner pointed to the two multi-million-dollar Texas verdicts and reportedly “substantial” out-of-court settlements to indicate Warner-Lambert’s culpability and where he thought future Rezulin litigation could go.“Once you prove causation these were not
happy jurors when it came to the conduct of Warner-Lambert,” Jenner said.“The [George] verdict is of limited, if any value to the defendant. Show me a case that says Warner-Lambert acted responsibly and that there was causation,” he said. “You can’t.” However, Pfizer spokesman Fateaux said “one of the important things” to bear in mind is the context of “the whole thing.” “I think that when you look at Rezulin, you’ll see that it was an innovative drug used to treat about 2 million people with Type II diabetes, and that it was effective for many people,” Fateaux said.“I think you’ll see that the company appropriately considered the risk of liver injury … when against the backdrop of all the people treated, there were fewer than 100 reports of serious liver injury during the three years the drug was on the market,” he added.Pfizer has acknowledged 90 liver failures, 63 deaths and seven liver transplants attributable to Rezulin.“While the company is prepared to pay reasonable compensation to the relatively small number of claimants with injuries demonstrably caused by Rezulin, we will vigorously defend the vast majority of cases in which the plaintiffs’ injuries, if any, cannot be reasonably attributed to the medication,” Fateaux reiterated from a company statement.Rezulin was the first in a new class of oral antidiabetic agents, thiazolidinediones, commercially known as glitazones, which enhance the body’s sensitivity to its own insulin and reduce the amount of sugar produced in the liver, while not lowering blood sugar to dangerously low levels.However, the drug was withdrawn from the market after it was discovered to produce serious side effects in some patients. Two alternative glitazones remain on the market: Avandia (rosiglitazone maleate), developed and marketed by GlaxoSmithKline, which the FDA approved in May 1999; and Actos (pioglitazone hydrochloride), developed and marketed by Eli Lilly & Co., of Indianapolis, Ind., and the Lincolnshire, Ill.-based Takeda Pharmaceuticals America Inc., which the FDA approved in July 1999.