Our predictions for Actos are coming true and the future of the drug is at risk.

With the demise of Avandia, Actos is now the world's leading type II diabetes medication.

However, Actos has lost support just recently in France and Germany over bladder cancer concerns.

And new information on macular edema concerns add more risks. The US has increased warnings but has not moved to rescind approval.

In our March 2011 report, we made a few predictions about the future of Actos. The first prediction was that increased risk for bladder cancer, macular edema, bone fractures, and heart risks for younger patients would surface and cause problems for the brand, including its removal from the market. The removal has started in the EU.

The second prediction was that any further movement to restrict or rescrind support for Avandia would also cause problems for Actos since we do not believe the brand is strong enough to be the last TZD standing. The FDA is removing Avandia from US retail availability in November of this year. Therefore, we see even more increased scrutiny of Actos as the brand had never really been able to separate itself completely from comparisons to Avandia.

Now Actos goes off patent at the end of this year but Takeda needs Actos to survive well past patent expiration. Takeda has Actos in clinical trials for future indications including MS. So, if the product gets pulled completely, it will not be able to expand.

But patients with MS as well as other autoimmune diseases that Takeda is eyeing for Actos are at risk for bone fractures. So our third prediction is that if increases in bone fractures surface in enough numbers to catch the FDA's attention, it could end future trials and indications. Also MS patients are younger (the average age of diagnosis is 33). We may seen increases in heart-related problems in MS trials with Actos further complicating things.

Actos is a huge part of the Takeda portfolio and revenue. It's future seems at risk and those risks have accumulated quickly in the last 6 months or so. So does Actos in jeopardy mean Takeda is in jeopardy too?