Takeda Pharmaceuticals and its U.S. partner Eli Lilly currently face lawsuits from thousands of plaintiffs who allege the company hid the risks of Actos bladder cancer. Earlier this year, a federal jury in Louisiana ordered the two companies to pay more than $9 billion in damages to Terrence Allen, a former hardware-store manager from Attica, N.Y., who alleged he developed bladder cancer after taking Actos. Takeda and Eli Lilly were fighting, but just lost a bid to have the judge throw out the award.

This is the largest award a pharmaceutical company has been ordered to pay in one case. While all diabetes patients may face a slightly increased risk of bladder cancer, several studies have suggested that long-term Actos users face an increased risk. Evidence showed to jurors demonstrated the company knew the Actos bladder cancer link existed, but failed to warn doctors and patients.

Allen’s case is the first federal trial over claims that Actos causes bladder cancer. It is assumed that the verdict, which according to Bloomberg is the second-largest in the U.S. in 2014, is likely to be reduced upon appeal.

The Actos Bladder Cancer Lawsuit is Allen v. Takeda Pharmaceuticals North America Inc., Case No: 12-cv-00064, in the U.S. District Court for the Western District of Louisiana (Lafayette).

Actos History

Approved by the U.S. Food and Drug Administration (FDA) in July of 1999 to treat type-2 diabetes, Actos was jointly launched by Takeda U.S.A. and Eli Lilly. Actos is part of a class of insulin-sensitizing diabetes agents known as thiazolidinediones (TZDs). Actos “exerts its antihyperglycemic effect only in the presence of endogenous insulin,” so it is only used to treat type-2 diabetes.

According to court filings, Actos has generated more than $16 billion in sales since its release in 1999. There are a many medications available to treat type-2 diabetes, and Actos has a significant part of the market share. By 2011, Actos accounted for 27 percent of Takeda’s revenue.

However, it is believed that Takeda and Lilly knew, or should have known, about Actos’ connection to heart damage and bladder cancer before applying for and obtaining FDA approval. Numerous studies showed the link between Actos and congestive heart failure, but the warning label wasn’t updated until 2007, when Takeda was forced to do so by the FDA.

The FDA enforced the warning label based on a number of adverse event reports and studies. One such study was PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events). The three-year study, designed to evaluate cardiovascular events, found a higher percentage of bladder cancer cases in patients receiving Actos versus those taking other medications.

Then, in 2010, the FDA issued a Safety Announcement for Actos, stating it was “undertaking a review of the data from an ongoing, 10-year epidemiological study being conducted by Kaiser Permanente [the University of Pennsylvania and Division of Research at Kaiser Permanente Northern California] to evaluate the association between Actos and bladder cancer.” The study found that the longer Actos is used, the more pronounced the risk of bladder cancer. Several European countries in 2011 issued an Actos recall because of this research. However, it was reported that Takeda executives said in an emailed statement that the study “found no significant risk of bladder cancer in Actos patients or link between the duration of the drug’s use and the disease.”