"Findings demonstrate that there is no statistically significant increased risk of bladder cancer among patients ever exposed to pioglitazone," the company said in a statement issued last week.
These data will be shared with regulatory authorities around the world, including the US Food and Drug Administration, the European Medicines Agency (EMA), and the Japanese Ministry of Health and Welfare (MHLW), among others, the company says. Final results will be submitted for publication this year, it adds.
Lead author of the study, James D. Lewis, MD, MSCE, from the Center for Clinical Epidemiology and Biostatistics at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, told Medscape Medical News he could not comment further on the findings, as the study is pending publication.
Asked to comment, Anne Peters, MD, director, University of Southern California Clinical Diabetes Program, Los Angeles, said: "I think it is good for all that the postmarketing data show no increase in bladder-cancer rates associated with pioglitazone. It was and is a good drug for the treatment of type 2 diabetes. Hopefully, this will clear up some of the confusion."
The company has also simultaneously announced that it has responded to the judgment in a jury verdict returned on pioglitazone in April, which resulted in one of the largest awards in punitive damages ever issued, $9 billion.
This is the only bladder-cancer case to reach trial in the federal courts — Takeda has prevailed in all the other 5 pioglitazone bladder-cancer cases tried in state courts thus far.
"We respectfully disagree with the judgment and await a ruling on our motion for a new trial or, alternatively, a significantly reduced punitive-damage award," said Kenneth D. Greisman, senior vice president and general counsel, Takeda Pharmaceuticals USA, in a statement issued today.
What's the Story So Far?
Pioglitazone, a thiazolidinedione for the treatment of type 2 diabetes, has been associated with a number of adverse effects, including fractures and fluid retention, and is contraindicated in patients with class 3 or 4 heart failure.
But it has been the association with bladder cancer that has caused the most controversy.
Many countries have put warnings with regard to this side effect on the packaging, including the FDA, which in 2011 updated the pioglitazone label to warn against starting the drug in patients with active bladder cancer and to use caution if starting it in patients with a prior history of bladder cancer.
And some countries — including France and Germany — banned or severely restricted the use of pioglitazone for this reason.
Also, in India in 2013, the drug was suddenly withdrawn from the market, purportedly due to the risk for bladder cancer, although it was later reintroduced with a boxed warning after many doctors complained. The Indian government stipulated on reintroduction that it should not be used as a first-line treatment for diabetes and that it should carry a boxed warning relating to bladder cancer.
Although use of pioglitazone has declined since its introduction, it is now available generically and is still a useful option for the treatment of certain patients with type 2 diabetes. And because it is available generically, it is also a good choice for many patients in developing countries.
Doctors in India said it was a particularly useful drug for South Asian patients because they have a lot of insulin resistance. One physician told Medscape Medical News that pioglitazone was the "cornerstone" of treatment in most patients in India.
New Results Provide Reassurance, Says Company
Now Takeda is confident that there is no risk for bladder cancer with pioglitazone.
The new 10-year data find no association between the risk for bladder cancer and the duration of pioglitazone use, increased cumulative dose of pioglitazone, or the time since initiating pioglitazone, it states.
"The results of the study provide reassurance with regard to the use of pioglitazone and the risk of bladder cancer and further support the positive benefit/risk profile of the product," said Tom Harris, head, global regulatory affairs, Takeda.
Data from the 5-year interim analysis of this same study, published in 2011, did show a statistically significant increased risk for bladder cancer among patients who used pioglitazone for two or more years (Diabetes Care. 2011;34:916–922).
Anne Peters is on the advisory board of Medscape Diabetes & Endocrinology. She has served as a consultant for Amylin/Lilly; Abbott Diabetes Care; Becton, Dickinson and Co; Janssen Pharmaceuticals; Medtronic; Perrigo; Roche; Takeda Pharmaceuticals North America; and Sanofi; and served as a speaker or a member of a speaker's bureau for Amylin/Lilly and Novo Nordisk.
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Cite this: No Bladder-Cancer Risk With Pioglitazone, Says Takeda - Medscape - Sep 04, 2014.