Within six months of being prescribed, buying and taking the Type 2 diabetes drug Avandia, Puerto Rico resident Celenio Cruz-Santana filed a class action lawsuit against the drug’s maker, GlaxoSmithKline (GSK).
The allegation: GSK actively concealed information regarding the risks associated with the use of Avandia and related drugs Avandamet and Avandaryl, and misrepresented its products as safe for their intended use.
Cruz-Santana’s 2007 lawsuit became the first of many product liability lawsuits over Avandia and its side effects. In fact, since 2007, more than 50,000 Avandia lawsuits have been filed in state and federal court across the U.S., citing GlaxoSmithKline’s failure to inform patients about potentially life-threatening effects that have been linked to Avandia treatment.
Studies Spur Lawsuits
When Cruz-Santana brought the lawsuit against GSK in 2007, at least six million patients in the U.S. had used Avandia, generating more than $3 billion in global annual sales for the company. Several studies, however, implicated Avandia as a factor in cardiovascular death, severe liver toxicity and increased risk of bone fractures.
Cruz-Santana’s complaint, for example, cited a study published May 21, 2007, in the New England Journal of Medicine that showed Avandia “significantly increased the risk of heart attacks, compared with other diabetes drugs or placebo.”
Dr. Steven E. Nissen and Kathy Wolski authored the study, which is titled Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. They reviewed more than 40 clinical studies involving nearly 28,000 patients and found users of Avandia have a 43 percent increased risk of heart attack when compared with other diabetes drugs or placebos, according to the complaint.
Moreover, GSK’s own analysis submitted to the U.S. Food and Drug Administration (FDA) in August 2006 showed Avandia causes a 31 percent increased risk of heart attack, the complaint said.
Avandia Risk Cover-up
In the months following the study’s publication, GSK officials acknowledged that they had known of the drug’s potential heart attack risks since at least 2005.
GSK had data suggesting Avandia’s extensive heart problems but went to great lengths to keep those risks from the public.
But according to a 2010 New York Times article, documents show the company had data suggesting Avandia’s extensive heart problems almost as soon as the drug hit the market in 1999. The company, however, went to great lengths to keep those risks from the public.
“In one document, the company sought to quantify the lost sales that would result if Avandia’s cardiovascular safety risk ‘intensifies,’” The New York Times article said. “The cost: $600 million from 2002 to 2004 alone, the document stated.”
Regulators React to Avandia Concerns
As concerns surrounding Avandia’s potential to cause cardiovascular complications rose, European regulators stopped sales of Avandia in 2010. The FDA revised Avandia labels in September 2010 and February 2011 to indicate cardiovascular risks and forced GSK to pull Avandia from pharmacy shelves, making it available only through a special government program.
However, in 2013 GSK completed a multi-year trial called RECORD that the FDA had directed it to perform, and the trial reportedly found no risk for adverse cardiac outcomes. Based on that outcome, in late 2013 the FDA removed restrictions on the prescription and sale of Avandia.
Avandia Federal Multidistrict Litigation
Still, serious side effects — plus disclosures that GSK had tried to hide evidence from an internal study that showed Avandia was more dangerous than an alternative medication made by another company — have led patients who had adverse reactions to Avandia to file lawsuits against GSK.
Federal claims, including the class action brought by Cruz-Santana, were consolidated in Multidistrict Litigation (MDL) No. 1871 in the U.S. District Court, Eastern District of Pennsylvania.
The actions “arise from allegations that certain diabetes drugs manufactured by GSK — Avandia and/or two sister drugs containing Avandia (Avandamet and Avandaryl) — cause an increased risk of heart attack and other physical injury, and that GSK failed to provide adequate warnings concerning that risk,” the Judicial Panel on Multidistrict Litigation noted in its October 16, 2007, order. GSK denied these allegations.
The panel said “centralization . . . will eliminate duplicative discovery, avoid inconsistent rulings, and conserve the resources of the parties, their counsel and the judiciary.”
In November 2011, the federal judge presiding over the Avandia MDL appointed a mediator to help resolve pending MDL cases via settlements, while proceeding with litigation on others. Roughly three months later, in February 2012, the judge announced that the court was satisfied with the progress of settlements and would now focus on resolving remaining cases through litigation.
To save time and money, GSK has settled many cases out of court. An estimated 50,000 Avandia cases have been settled so far. Nearly 5,300 cases that were part of the MDL have been resolved, but half a dozen actions in the MDL remained pending as of August 15, 2017.
GSK 2010 Avandia Settlements
In 2010 alone, the company agreed to pay well over a half-billion dollars in settlements. These include:
GSK settled more than 700 Avandia lawsuits for about $60 million
The company settled an additional 5,700 lawsuits
GSK settled 10,000 more at a cost of $460 million
In early 2011, as the first federal Avandia trials began, GSK agreed to pay a reported $250 million to settle 5,500 claims that Avandia had resulted in death. Information about how much money any individual won in a settlement is hard to come by, as settlements often include confidentiality clauses that keep people from sharing details.
Future Avandia Litigation and Settlements
GSK has set aside funds in anticipation of future Avandia lawsuits. In January 2011, the company announced it was setting aside $3.4 billion to pay for future Avandia litigation and settlement costs.
Although GSK is expected to settle additional lawsuits out of court, the company is not expected to resolve them all outside of court. As of March 2017, 85 cases were still pending, and some may be tried before a jury.
U.S. Senate Investigates GlaxoSmithKline
From the beginning, GSK maintained publicly that Avandia is safe and effective when used appropriately. However, a report on a two-year investigation by the U.S. Senate Finance Committee in February 2010 accused GSK of failing to report another company-sponsored study, completed in November 2003, in which patients given Avandia had more heart problems than those given placebos.
The Senate investigation also revealed that GSK’s own 2006 meta-analysis of dozens of Avandia studies established that the drug increased the risk of serious heart problems by nearly a third.
The Sentate report concluded GSK knew of the cardiovascular dangers associated with Avandia and “took [steps] to create doubt regarding negative findings about the drug.” It urged the FDA to take Avandia off the market, but the agency declined to do so.
A few months later GSK came in for more censure when company documents uncovered by The New York Times revealed that in 1999, GSK set out to determine if Avandia was safer for the heart than Actos, a similar medication made by Takeda. Not only was Avandia found to be no better than Actos, it was actually riskier. But instead of publishing the study’s outcomes, the company covered them up, according to The Times.
GlaxoSmithKline Federal Fraud Settlement
In July 2012, GSK pleaded guilty to federal charges that it failed to report clinical data on Avandia and that it misbranded and unlawfully promoted the drugs Paxil and Wellbutrin for off-label use. The company reached an agreement with the U.S. Department of Justice to pay a $3 billion settlement.
At the time, the Justice Department said the resolution was “the largest health care fraud settlement in U.S. history and the largest payment ever by a drug company.”
“Today’s multi-billion dollar settlement is unprecedented in both size and scope.”
- then Deputy Attorney General James M. Cole said in 2012
According to the U.S. government, between 2001 and 2007, GSK omitted certain safety data about Avandia in reports to the FDA. The reports are meant to allow the federal agency to determine if a drug continues to be safe for its approved uses and to identify drug safety trends.
Among the missing information was data regarding certain post-marketing studies. The company also failed to include data regarding two studies conducted in response to European regulators’ concerns about the cardiovascular safety of Avandia.
“Since 2007, the FDA has added two black box warnings to the Avandia label to alert physicians about the potential increased risk of (1) congestive heart failure, and (2) myocardial infarction (heart attack),” the Justice Department said. “GSK has agreed to plead guilty to failing to report data to the FDA and has agreed to pay a criminal fine in the amount of $242,612,800 for its unlawful conduct concerning Avandia.”
AVANDIA is not recommended in patients with symptomatic heart failure. Initiation of AVANDIA in patients with established NYHA Class III or IV heart failure is contraindicated. [See Contraindications (4), Warnings and Precautions (5.1).]
GlaxoSmithKline State Lawsuit Settlements
Thirty-eight state attorneys general sued GSK over its marketing of Avandia. They alleged that the company had, without evidence, represented Avandia as a medication for lowering cholesterol, and promoted it for having cardiovascular benefits when in fact it might have increased cardiovascular risks.
GSK also promised to change the marketing and promotion of all of its diabetes medications, though it did not admit to being guilty of any wrongdoing.
In November 2012, GSK agreed to pay $90 million to be divided among:
- District of Columbia
- New Jersey
- North Carolina
- North Dakota
- Rhode Island
- South Dakota
Other GSK State Settlements
Nine states opted out of the earlier action against GSK. In July 2013, the company agreed to pay Louisiana $45 million to settle lawsuits that it improperly marketed Avandia and other drugs in that state. Louisiana said the money would go to its Medicaid program. Meanwhile, attorneys general in Kentucky, Mississippi, Maryland, South Carolina, New Mexico, West Virginia and Utah divided a settlement of $229 million.
GSK said it was settling to avoid a lengthy trial, and that it was not admitting any liability for the same charges as states made in the earlier case.
Humana’s Lawsuit Against GlaxoSmithKline
Health care insurer Humana Medical Plans sued GSK in November 2010. Humana cited GSK’s settlements with individuals who sued the company. It said that dozens of those patients were covered under Humana’s Medicare Advantage insurance, and that the federal Medicare Secondary Payer Act gave private insurers a right to sue for reimbursement of the health care costs they paid as benefits.
The Third U.S. Circuit Court of Appeals ruled for Humana. GSK attempted to appeal to the U.S. Supreme Court, but the court declined to consider the case.
Emily Miller holds five Health Literacy certificates from the Centers for Disease Control and Prevention as well as a Bachelor of Science in Journalism from the University of Florida. She is a member of The Alliance of Professional Health Advocates, the American Association for the Advancement of Science and the Society for Technical Communication. Emily was diagnosed with a chronic illness as a child and has firsthand experience with many of the topics she writes about as a member of the Drugwatch team. She is an award-winning journalist who has reported on health and legal news for reputable organizations, including the South Florida Sun Sentinel, San Antonio Express-News, UF Health News and Reporters Committee for Freedom of the Press. She draws on her background as both a patient and a journalist to help readers understand complex health and legal topics.