Diabetes Drug Could Spur Next Big Pharmaceutical Litigation

By Christa Zevitas

A drug designed to stabilize diabetes could be the next big wave of pharmaceutical litigation, plaintiffs' attorneys nationwide predict.

Users of Rezulin have experienced liver toxicity, congestive heart failure and even death, according to the FDA. The drug netted more than $1.8 billion before it was taken off the market in March 2000.

Attorney Joseph Santoli says the drug's manufacturer — Warner-Lambert of Morris Plains, N.J. — knew that Rezulin could cause liver failure and cardiac toxicity long before it fought for FDA approval. Not only did the pharmaceutical giant fail to share this knowledge with the FDA, it also failed to warn the public of the risks when the drug went on the market, Santoli says.

Some of Santoli's cases allege that the company had ties to a top diabetes researcher who was instrumental in getting accelerated FDA approval for the drug.

Although the majority of Rezulin suits are in the beginning stages of litigation, plaintiffs' lawyers say these cases hold the potential for large compensatory and punitive awards.

"We believe these cases are extremely strong," says Santoli, whose two-lawyer firm in Ridgewood, N.J., is handling more than 200 Rezulin cases. "The drug is so defective and Warner-Lambert knew this while they were advocating its approval. For example, when Warner-Lambert made its presentation to the FDA's Advisory Committee, it claimed that Rezulin did not increase cardiac mass or impair cardiac function. It made this representation despite [a company-funded study that] demonstrated the propensity of Rezulin to cause heart damage."

Houston attorneys Jeb Wait and David Mathews are so confident in these cases that they decided to devote their entire caseload to Rezulin suits last year.

What's more, their firm hired two additional associates just to work on Rezulin litigation. It also hired a full-time physician to screen potential Rezulin plaintiffs and a full-time computer expert to find internal company documents that bolster the plaintiffs' suits.

Santoli believes this level of commitment indicates the strength of Rezulin litigation.

"At halfway through discovery, the Texas attorneys are furthest along in this litigation and therefore know more than anyone else," he says.

He adds that the numbers of Rezulin cases being filed further suggest that it has blockbuster potential.

Thus far, Santoli estimates that at least 200 individual suits have been filed nationwide. Furthermore, lawyers in Pennsylvania, West Virginia, New Jersey, New York and Massachusetts have filed Rezulin class actions and others in Washington, D.C., and Delaware have filed numerous wrongful death suits against Warner-Lambert.

"I believe this is just the tip of the iceberg," says Santoli, stressing that between 500,000 and 1.5 million people took Rezulin during the three years it was on the market. "The FDA has reported [more than 60] Rezulin-related deaths, but for every liver failure reported to them there could be anywhere from 10 to 100 more that aren't reported. This is true in just about any toxic [pharmaceutical] case."

Mathews agrees, saying his firm is currently screening 5,000 potential plaintiffs who believe they're entitled to medical monitoring and, in some cases, damages.

But plaintiffs' attorneys offer a warning: Take one of these cases only if you're prepared for battle against a large pharmaceutical company and all that can entail — stonewalling during discovery and other pretrial tactics that drive up the cost of litigation in terms of both money and manpower.

Furthermore, they say it's not wise to accept a Rezulin case unless you plan to take on several more.

"If you want to take just one or two of these cases, it's not going to be economically feasible unless you associate with other firms that are handling this litigation full-time," says Wait. He adds that that Rezulin litigation will most likely be economically worthwhile for his firm because they expect to have "hundreds, if not thousands, of cases."

Defense attorneys for Warner-Lambert couldn't be reached for comment.

On Jan. 29, 1997, the FDA granted Rezulin approval to treat Type 2 diabetes, the less severe form of the disease for which patients don't generally require outside sources of insulin.

The approval process took only six months, compared to the average approval process of more than 14 months, according to Santoli. He says the FDA claimed that it fast-tracked Rezulin's approval because it was necessary to help patients who weren't responding to older diabetes drugs.

Yet plaintiffs' attorneys emphasize that long before the FDA's approval, scientists had documented concerns about the drug's potential to cause heart and liver damage. As far back as the mid-1990s, FDA pharmacologists found that after they gave healthy animals doses of Rezulin, their hearts became discolored and overweight.

Those pharmacologists wrote that "these changes were drug-related, and were responsible for the early mortality in both sexes [of rats and monkeys]," according to a Los Angeles Times series on Rezulin.

Plus, in a written evaluation dated Oct. 9, 1996, one of the FDA's chief medical officers responsible for Rezulin research — Dr. John L. Gueriguian — recommended against the drug's approval. Gueriguian's evaluation cited the drug's potential to harm the liver and the heart.

"After Warner-Lambert complained to FDA officials, Dr. Gueriguian was removed from the Rezulin review," according to a class action complaint that Santoli filed.

The complaint also says that "the FDA Advisory Committee was never told that 11 research patients had suffered potentially life-threatening liver injuries" before the committee voted 8-0 to recommend that the FDA approve Rezulin without any warning about liver toxicity.

According to the Los Angeles Times series, many of the FDA scientists who were advocating for Rezulin's approval were paid consultants to Warner-Lambert.

On Nov. 3, 1997, just 10 months after the company began marketing Rezulin, it announced the first change to the drug's warning label. The label change recommended that users undergo routine liver enzyme testing within the first one to two months of taking Rezulin. A month later, the drug was banned in Britain.

In the U.S., Rezulin underwent three more label changes over a period of almost two years; with each new label, the company recommended more stringent liver enzyme testing.

Santoli predicts that the company will defend its cases by arguing that it changed Rezulin's warning labels several times. But, he adds, that defense is "weak because the FDA was insisting upon those label changes. They were essentially telling the company 'You change your label or withdraw the drug from the market.'

"Plus, they didn't warn of the serious risks," Santoli adds. "Only in the last letter [to doctors] did they acknowledge those risks — and that letter went out shortly before the drug was taken off the market."

According to the Los Angeles Times series, on May 17, 1998, a 55-year old woman who was participating in a study of Rezulin by the National Institutes of Health suffered liver failure and died after taking the drug.

"Her death prompted senior NIH officials to banish Rezulin in June 1998 from the study," the article reads.

Santoli adds that the woman wasn't a diabetic.

Santoli's complaint says that "Warner-Lambert announced that the death was 'apparently due to complications unrelated [to Rezulin],' but Warner-Lambert knew or disregarded that NIH doctors had decided that the most likely cause of liver failure was Rezulin."

Upon the FDA's request, Warner-Lambert withdrew Rezulin from the market on March 21, 2000. At that time, the FDA came out with a press release that said Rezulin was more toxic to the liver than its two alternatives, Avandia and Actos.

Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said in the press release that "the pre-marketing clinical data and post-marketing safety data from Rezulin indicate that continued use of Rezulin now poses an unacceptable risk to patients."

Santoli adds that "since its withdrawal, previously concealed adverse information regarding Rezulin has emerged.

"For instance, the FDA's senior epidemiologist has estimated that 20 Rezulin patients a month are suffering from liver failure," he says. "That occurred at least two years before Rezulin was withdrawn from the market. And the FDA is now investigating whether Warner-Lambert concealed findings of liver toxicity in 1994 clinical trials."

So far, plaintiffs' lawyers say the strongest cases are those that involve plaintiffs who have allegedly suffered liver damage from Rezulin.

The FDA has already established that Rezulin can cause liver failure, damage and elevated liver enzymes in the blood. Last year, an FDA study found that:

• An estimated 430 Rezulin patients have suffered liver failure;

• Rezulin users increase their risk of liver failure by 1,200 times by taking Rezulin;

• One out of every 1,800 Rezulin patients could suffer liver failure; and

• Regular liver monitoring is no guarantee of safety because Rezulin can quickly and unpredictably attack the liver.

"Liver cases are strong because diabetics don't inherently have liver problems," says Wait, who's also a physician. He believes the "perfect Rezulin plaintiff" is a non-drinker without a history of liver problems who suddenly experiences an elevated liver enzyme test after taking Rezulin.

He adds that he "feels very strongly that liver cases will be easier to prove than heart cases because diabetics inherently have heart problems. It's therefore going to be tougher to prove that a plaintiff's cardiovascular problems weren't caused by the disease itself."

For this reason, Santoli says he's not taking any heart damage or heart failure cases until scientific research definitively links Rezulin to cardiovascular problems. "We've been approached with between 200 and 300 claims alleging Rezulin caused heart failure and death, but haven't agreed to take any of those cases," Santoli says.

Wait and Mathews, however, are taking both types of lawsuits.

Mathews notes that Rezulin has been proven to cause excessive weight gain, which "can clearly be an underlying cause of other heart problems.

"So a plaintiff without any prior heart problems before taking Rezulin who witnesses a sudden onset of weight gain and sudden heart failure afterwards could have a legitimate damages case," he says. "Thus far, I've seen dozens of these."

Wait predicts that the strongest plaintiffs' strategy in Rezulin litigation will be that "Warner-Lambert pulled the wool over the FDA's eyes by not providing all the data they had regarding Rezulin-related liver problems.

"We have very good reason to believe that incriminating evidence against Warner-Lambert is out there," says Wait, noting that a court gag order prohibits him from talking in greater detail about this evidence. "We believe that the single driving force behind the company's [pushing for fast-track approval] was money. In a 1996 annual report, the company said Rezulin was a potential billion-dollar blockbuster drug. It knew if Rezulin could penetrate even a small percentage of the 15 to 16 million Type 2 diabetics in the U.S., the company could generate billions of dollars."

If cases reach trial, Wait believes that Rezulin verdicts could mirror verdicts in litigation involving the diet drug fen-phen. The first-ever fen-phen case to go to trial — which plaintiffs' lawyers across the nation labeled a "weak" lawsuit — resulted in a $20 million punitive damages verdict against pharmaceutical giant American Home Products. (See, "$23 Million Fen-Phen Verdict May Open Doors to Bigger Settlements," 99 LWUSA 830, Search Words for LWUSA Archives: Zevitas and Lovett.)

The verdict was intended to punish the company for putting profits ahead of people in its marketing and labeling of the diet drug.