The drug Actos (pioglitazone) has been one of the most financially successful drugs in the history of diabetes treatment. It first went on sale in the U.S. in 1999. Since then it has been estimated that sales of Actos have exceeded $24 billion. That is a LOT of money.
But this week the manufacturer of Actos, Takeda Pharmaceutical, announced that it would settle thousands of lawsuits against this medication. Although the company isn’t admitting any liability in these lawsuits, it will pay out roughly $2.4 billion to people who took the drug or to their surviving families. The reason: Actos is linked to bladder cancer.
What makes this case unusual is that Actos remains on the market. In a new release we were told that, “Takeda’s decision to settle does not change the company’s continued commitment to Actos.” Say what? The company is prepared to pay billions to settle lawsuits with people who developed cancer but they are continuing to market Actos to people with diabetes. Does this make sense to you?
What Happened and Where Is the FDA?
On September 17, 2010 the FDA announced that it was:
“…reviewing data from an ongoing, ten-year epidemiological study designed to evaluate whether Actos (pioglitazone), is associated with an increased risk of bladder cancer. Findings from studies in animals and humans suggest this is a potential safety risk that needs further study.”
On June 15, 2011 (roughly 12 years after Actos started appearing on pharmacy shelves) the FDA announced that people who had taken Actos for more than a year might be at greater risk of bladder cancer. The agency warned that anyone with bladder cancer should avoid the drug, and it should be used “with caution” by those who had bladder cancer in the past.
On August 9, 2012, the Journal of the National Cancer Institute released a report suggesting that there was indeed a worrisome link to bladder cancer. Investigators reviewed records from more than 60,000 people with type 2 diabetes in the United Kingdom. Those who took Actos were two to three times more likely to be diagnosed with bladder cancer compared to those taking other antidiabetes drugs.
Actos Banned in France, Germany and India but Not in the U.S.
By 2011, regulators in France and Germany were convinced that Actos posed enough of a risk that they banned the drug. India followed with its own ban in 2013. But the U.S. Food and Drug Administration was content with a warning. It is written in classical FDA bureaucratic language:
“…There are insufficient data to determine whether pioglitazone is a tumor promoter for urinary bladder tumors. Consequently, ACTOS should not be used in patients with active bladder cancer and the benefits of glycemic control versus unknown risks for cancer recurrence with ACTOS should be considered in patients with a prior history of bladder cancer.”
There is also this in the official prescribing information:
“Urinary Bladder Tumors
Tumors were observed in the urinary bladder of male rats in the two-year carcinogenicity study [see NONCLINICAL TOXICOLOGY (13.1)]. In two 3-year trials in which ACTOS was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of bladder cancer in patients taking ACTOS compared to 5/3679 (0.14%) in patients not taking ACTOS. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on ACTOS and two (0.05%) cases on placebo. There are too few events of bladder cancer to establish causality.”
Have your eyes glazed over? It’s hardly any wonder that patients and prescribers might not have paid much attention to this information. Six vs. two cases of bladder cancer seems like a trivial risk. And the FDA seems almost reassuring in its conclusion that “There are too few events of bladder cancer to establish causality.”
The agency did not put a bladder cancer concern in the black box warning that already exists for Actos about the drug causing or exacerbating congestive heart failure. Bottom line: the FDA seems to have minimized the risk of bladder cancer. It’s hardly any wonder that doctors continued to prescribe the drug.
Billion Dollar Settlement
It must come as a tremendous shock to FDA officials to learn that there are roughly 9,000 bladder cancer claims against the manufacturer of Actos and that the company is willing to pay $2.4 billion to make them go away. This is one of the largest product-liability settlements in the history of the drug industry. Perhaps even more astonishing, Actos remains on the market with FDA approval.
So, here’s our question: Who is the FDA protecting? The American public or the drug company?
If regulators in France, Germany and India have all deduced that Actos is so dangerous that it should not be sold in their countries, why is the FDA continuing to allow its sale in the U.S., even after a billion dollar settlement?
We would value your thoughts on this controversial topic. Have you taken Actos? What was your experience? You can contribute a comment below in the “ADD MY THOUGHTS” section. And please vote on this article at the top of this page.