More American women die from heart disease than any other cause, and Margaret Clark wanted to cut her chances of getting it. So in 2002, the North Charleston, S.C., woman did what millions of otherwise healthy women have done and started taking Pfizer's
statin drug Lipitor to lower her cholesterol, in hopes of reducing her risk for coronary artery disease. She was 46 at the time.
But after a decade on Lipitor, she developed another medical condition, Type 2 diabetes
, which could lead to heart disease—the condition she took the drug to prevent. She said in court filings that she developed diabetes despite maintaining a healthy diet and body mass and an active lifestyle.
The mass-tort litigation could draw new attention to risks associated with statin drugs, as millions more Americans consider whether to take them under new guidelines expanding the eligible population.
Clark became one of the first of several hundred women across the country to sue New York City-based Pfizer in federal court, alleging the company knew from early clinical trials that women taking Lipitor faced an increased risk of developing Type 2 diabetes and that Pfizer's warning label did not clearly describe that risk.
H. Blair Hahn, an attorney with South Carolina-based Richardson, Patrick, Westbrook & Brickman, the lead law firm in the litigation, said clinical evidence shows that Lipitor can increase women's risk of developing diabetes by as much as 700%. “They knew that when they launched Lipitor,” he said. “That information was in the new drug application, but it was not spelled out directly.”
In February, hundreds of Lipitor-related product liability lawsuits, including Clark's, alleging fraud and negligence by Pfizer were officially certified as a mass tort and consolidated in the U.S. District Court of South Carolina in Charleston by Judge Richard Gergel. A mass tort is similar to a class-action case, except that each plaintiff's allegation is judged separately. Similar product liability cases against Lipitor are piling up in many state courts, particularly in California.
The first of the federal Lipitor cases is scheduled to go to trial in mid-2015, though the two sides haven't yet chosen the initial plaintiffs. In mass-tort cases, such “bellwether” trials help companies and plaintiffs evaluate the strength of the evidence and evaluate settlement options for the remaining cases.
The Food and Drug Administration
says taking statins, including Lipitor, has been linked to reported increases in blood-sugar levels and a small increased risk of developing diabetes.
Although the FDA says the risk of diabetes associated with statin use applies to both men and women, attorneys have filed cases on behalf of only female clients. That's because the way women's bodies metabolize Lipitor makes them more susceptible to diabetes risk, Hahn said.
Pfizer denies that its blockbuster drug raises the risk of diabetes in women or men. It also argues that Lipitor's label is accurate and that it was approved by the FDA. “There is an overwhelming consensus in the medical community regarding the benefits of Lipitor,” a Pfizer spokesman said. “The safety and efficacy of Lipitor is supported by nearly two decades of research.”
The outcome of these cases is being closely watched as a sign of whether Pfizer and other drugmakers face significant legal challenges related to statins. The litigation also could draw new public attention to the risks associated with statin drugs, as millions more Americans consider whether to take this class of cholesterol-reducing products under new guidelines issued by the American Heart Association and the American College of Cardiology last year.
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In late 2013, the two organizations jointly published new clinical guidelines that recommended statins for about 10 million more Americans who do not have pre-existing heart disease. The new guidelines mean that 49% of the U.S. adult population will be eligible to take statins, up from the current 38%, according to an analysis published April 10 in the New England Journal of Medicine.
Some experts question the wisdom of efforts to expand statin drug use among healthy people at low risk for heart disease.
“It's very attractive to think that you can take a pill for good health, but unfortunately, it is not supported by the evidence,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco Medical Center who is editor of JAMA Internal Medicine.
The clinical evidence for healthy women with high cholesterol to take statins is thinner than for men, she added, because women tend to develop heart disease about a decade later in life than men, while facing the heightened risk of diabetes in the interim.
Most statins present the same type of diabetes risk as Lipitor, according to the FDA. But while advertisements can be found online for litigation against other statins, such as AstraZeneca's Crestor and Merck's Zocor, none of those cases have reached the critical stage of generating enough plaintiffs to apply for national multi-district litigation status, which the Lipitor litigation received in February.
“The reason we are focused on Lipitor is because it is the largest-selling drug in the world,” Hahn said. “But most of the statins have the same problem that Lipitor does.”
The FDA first approved Lipitor for sale in 1996. Four years later, Pfizer acquired all rights to the drug by purchasing its corporate inventors. Lipitor went on to become the most widely prescribed drug of its era, and doctors have given it to 29 million Americans to date. Worldwide sales of Lipitor peaked at nearly $13 billion in 2006, before branded competitor drugs and the expiration of Lipitor's patents globally shrank the drug's price and profitability. Pfizer reported $2.3 billion in Lipitor sales last year.
Yet almost 20 years after the drug's initial approval, plaintiffs like Clark are saying the company withheld critical information on diabetes that, at the very least, could have helped them watch for onset of the disease.
A key issue in “failure-to-warn” litigation like this is whether Pfizer knew, or should have known from clinical trials, about Lipitor's risk of causing blood-sugar changes that trigger diabetes. “The question is whether Pfizer already knew this and concealed it,” said Kay Dickersin, director of the Center for Clinical Trials at Johns Hopkins Bloomberg School of Public Health.
If the clinical trials provided evidence of a heightened risk, Pfizer could be held liable. Plaintiffs in failure-to-warn cases typically try to establish that a “signal” was detected in the drug's clinical trials that the drug manufacturer either ignored or concealed. But experts disagree about how big a spike in the data is considered a signal for increased risk, Dickersin said.
Since the Lipitor cases are new and little evidence has been made public yet, it's difficult to assess the merits of the cases. Even armed with strong evidence from clinical studies, plaintiffs often find it difficult to prove that a drug caused an individual's medical condition.
Attorneys for Pfizer declined to comment on their litigation strategy. But the company has said in written statements and legal filings that diabetes and heart disease share numerous risk factors, and that cholesterol-cutting drugs such as Lipitor are often prescribed to people who are already at risk for developing diabetes. “We intend to vigorously defend the allegations,” Pfizer said in a written statement responding to questions from Modern Healthcare.
But one of the attorneys suing Pfizer said the plaintiffs can overcome the perception of Lipitor's safety.
“Did you believe that Vioxx, one of the largest selling drugs at the time, caused heart attacks and strokes? A lot of people didn't believe that at first, either,” said Chris Coffin, a partner at Pendley Baudin & Coffin in Plaquemine, La., who is representing Lipitor plaintiffs. “When the science says there is a negative outcome—and the science clearly shows that (for Lipitor)—it's hard to refute.”
The lawsuits also challenge the adequacy of Pfizer's current 20-page consumer brochure for Lipitor. In 2011, an analysis of published medical literature and drug-trial data led the FDA to require Pfizer and other statin makers to update their product labels and brochures to reflect the small risk of increased blood-sugar levels. Pfizer responded by disclosing that the drug may affect “HbA1c and fasting serum glucose levels,” which are two measures of sugar in the blood.
Clark and other plaintiffs claim Pfizer's language was intentionally vague to hide the risk of diabetes. Their lawyers point out that the wording in Pfizer's label change was more obscure than the wording in label changes issued by the makers of other statin drugs. AstraZeneca's label for its statin drug Crestor warns explicitly that increases in glucose levels “may exceed the threshold for the diagnosis of diabetes mellitus.”
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Published statements by the FDA, however, offer ammunition to both sides.
The FDA's official “Drug Safety Communication” warned: “Increases in blood sugar levels have been reported with statin use.” A section on the page intended for healthcare professionals repeats verbatim the language on the Lipitor label.
Yet under the FDA's “For Consumers” Web page, the agency wrote: “People being treated with statins may have an increased risk of raised blood-sugar levels and the development of Type 2 diabetes.” All the FDA warnings apply to both men and women taking statins.
In a 2012 post on the FDA website that remains online today, Dr. Amy Egan, deputy director for safety in the FDA's Division of Metabolism and Endocrinology Products, wrote that the new information about increased diabetes risk “should not scare people off statins.”
However, Johns Hopkins' Dickersin said the Lipitor litigation may add to consumer uncertainty about taking statin drugs. “It's a really tough thing for the average consumer,” she said.Follow Joe Carlson on Twitter: @MHJCarlson