Memorandum
Takeda announced last week that full results from a ten-year epidemiological observational study demonstrated no statistically significant increased risk of bladder cancer among patients treated with Actos (pioglitazone) or combinations containing pioglitazone; additionally, there was no finding of increased risk with longer duration of exposure or higher cumulative dose. The data has been submitted to regulatory authorities including the FDA and the EMA, and final results will be submitted for publication in a scientific journal later in 2014. The FDA updated the label and medication guides for pioglitazone-containing products in 2011 to include a warning that the use of such drugs for longer than one year could be associated with increased bladder cancer risk; that decision was based on an interim analysis of five-year results from this study, which found that increased dose and duration of pioglitazone use did lead to a higher risk (of nominal statistical significance) of bladder cancer. Meanwhile, sales of pioglitazone-containing drugs have fallen sharply since the controversy came to light, mostly because of the move to generic status, of course – Actos brought in only ~$120 million in revenue in F1Q14 compared to over $1 billion each quarter during its blockbuster days and this would have been expected regardless of controversies over cancer, though the steep fall wouldn’t have happened as quickly had the controversy not arise. To boot, Takeda and former Actos co-promoter Lilly are currently facing thousands of lawsuits alleging that the companies hid cancer risks associated with the drug from the public. We believe that this case perfectly illustrates the risks of interim data disclosure from large epidemiological studies; at a recent FDA hearing regarding interim disclosure of results from cardiovascular outcomes trials, many speakers raised concerns about the unreliability of interim data and the potential negative impact of interim disclosure on the public and regulatory perception of a drug, particularly since sensationalistic media headlines tend not to capture the full nuances of complex study results.