Actos Bladder Cancer Risk–Known by the EMA and the Manufacturer Since 2000

In Big Pharma’s constant search for the magic pill, the one that promises relief or a cure for chronic debilitating disease, concerns about side effects, even potentially fatal ones are often dismissed as aberrations, anomalies or not clinically significant. For type 2 diabetics, the two latest magic pills that promised relief are Avandia and Actos. In order to get these latest, greatest Holy Grails past regulators, Pharma must submit proof of safety and efficacy. Proof of safety mainly comes in the form of animal studies and clinical trials. However, these studies and trials are usually conducted on small samples over short periods of time. They cannot and do not mimic real world experience.

But, sometimes the potentially ugly complications reveal themselves during those studies. It has now been disclosed that the risk of bladder cancer was raised in Europe when Takeda Pharmaceuticals sought regulatory approval to market Actos in Europe. The EMA admits a potential risk of bladder cancer was identified during animal studies submitted to the European Medicines Agency (EMA) in 2000. During animal trials male rats exposed to Actos developed bladder cancer but, “the evidence did not point to a risk in humans.”

I don’t know about you but, statements like this made by Big Pharma make me crazy. We tested the drug on rats and they developed bladder cancer. But, you should ignore those findings because that doesn’t necessarily mean humans will get bladder cancer. Well then why are you doing animal testing? Since we all know they can’t sell the magic pill without doing the studies, the answer begs the question: Where does that leave us, the consuming public?

It seems that the EMA allowed Takeda’s claimed disconnect between rats developing bladder cancer and humans being susceptible to the same risk to pass unnoticed. They let them market the drug on the promise they would conduct a population based study on the long-term safety of pioglitazone (Actos) which was conducted here in the US at Kaiser Permanent in California. That study is still ongoing but, preliminary result of the study shows an increased risk in humans of developing bladder cancer. Seems Actos agrees with neither rat nor human bladders.

In a separate clinical trial (PROactive) more bladder cancer cases were reported for Actos (pioglitazone) than placebo (sugar pill) and there has been a higher than expected number of reports of bladder cancer in patients taking Actos in the EU and the United States. My question is just how much bladder cancer is “expected?” I guess the EMA finally felt that the “signal” warranted a “full review.”

During that “review” new data emerged from a study in France which, not surprisingly, pointed to an increased risk of bladder cancer for Actos takers. Good on the French. That one study was enough for them to suspend the sale (fancy words for recall) of Actos in France. Germany and Luxembourg followed and informed doctors to quit prescribing the medicine to patients. After looking at all the evidence, the EMA found there to be an increased risk of bladder cancer for patients taking Actos. While they left the drug on the market, they said that only a small portion of type 2 diabetes sufferers were candidates for taking the medicine. Only those patients whose diabetes did not respond to other forms of treatment should consider Actos. They went on to say that when prescribed, Actos should be given at the lowest possible effective dose and for the shortest duration necessary. Elderly patients seem to be at the highest risk.

All the while, you could go to your favorite CVS, Walgreens or Duane Reade and fill a prescription for Actos here in the USA with no limitations. Why does the FDA consistently seem to lag behind foreign regulatory agencies in performing drug safety surveillance?

In response to the uproar in Europe, the FDA has issued safety alerts but, they simply say that the only patients who should not take Actos at all are patients who have active bladder cancer. Now that’s groundbreaking advice! They say if you have had bladder cancer you should “use caution” when taking Actos. Just how does a patient taking Actos, “use caution?” Since they say, “If while on the drug you start urinating blood to call your doctor immediately,” I guess using caution means if you develop bladder cancer while taking Actos, get cancer treatment quickly. Again, that’s some comforting advice.

I don’t know about you but, to me that seems absurd. Luckily, I don’t suffer from diabetes and I’m sure those who do are desperate for medication that will keep it under control, however, the two latest, greatest magic pills that promised this either exposed you to death from a heart attack (Avandia) or bladder cancer (Actos). There’s gotta be a better way to regulate these magic pill makers.