Let’s get this over with already

Let’s get this over with already

This past Friday the FDA stated they had begun a safety review of Actos based on a possible link to bladder cancer. According to a statement issued by the agency:


“The U.S. Food and Drug Administration today announced it has begun a safety review of the diabetes drug Actos (pioglitazone), after receiving preliminary results from a long-term observational study designed to evaluate the risk of bladder cancer associated with use of this drug.


The preliminary results are based on five-year data from an ongoing, 10-year observational study by the manufacturer, Takeda Pharmaceuticals North America Inc., San Diego. These early results showed no overall association between Actos exposure and risk of bladder cancer. However, there was an increased risk of bladder cancer in patients with the longest exposure to Actos and in those with the highest cumulative dose of the drug.


At this time, the FDA’s review is ongoing. The agency has not concluded that Actos increases the risk of bladder cancer.”


This news is just the latest blow to Actos as the other reports have indicated Actos may have the same adverse cardiovascular events as Avandia, the much maligned TZD from GlaxoSmithKline (NYSE:GSK).


As has become standard operating procedure the agency does not indicate exactly what risk they are seeing and adds to the confusion by stating they have not concluded Actos increases the risk of bladder cancer. The obvious question then becomes why did the agency find it necessary to conduct the review and take the additional step of issuing a press release about the review? Was it really necessary to alarm an already alarmed patient population?


Since the Avandia controversy began, the FDA has had one misstep after another. Unless the FDA has been hiding in a cave and are oblivious to what’s going on in the real world, a strong possibility given that the agency appears increasing clueless, they should know that Actos was the most likely replacement when Avandia became tainted. It’s no accident Actos sales increased after Avandia usage was associated with possible increased cardiovascular risk. Both Avandia and Actos are TZD’s, which prior to all this news appeared to particularly effective at treating patients with type 2 diabetes.


That was until we discovered that both drugs were associated with an increased incidence of bone fractures, a development that came to our attention after both drugs had been on the market for nearly 7 years. Next was the famous meta-analysis that seemed to indicate that Avandia increased the risk of adverse cardiovascular events, an event that at first seem to affect only Avandia but as mentioned earlier now has touched Actos. Which brings us to the present with Actos and bladder cancer; an event not yet associated with Avandia but given the way things are going probably will be.


Watching this with great delight are the executives at Merck (NYSE:MRK) who’s drug Januvia continues the longest and luckiest streak ever in diabetes drug history. With physicians running out of options Januvia has become the drug of choice to replace Avandia and now Actos.


Diabetic Investor also sees this news as a major plus for GLP-1 therapy which continues to gain acceptance with physicians and patients.


All that aside Diabetic Investor wonders just why the FDA, with the growing list of issues surrounding TZD’s, has not asked the drugs to be pulled from the market. Are they waiting for even more data to show the drugs are linked with even more adverse events?  Has their mission changed from protecting the public to scaring the living daylights out of the millions of patients who take these drugs each and every day? Is their goal to cause physicians even more grief and further limit the options they have to fight diabetes?


Diabetic Investor has long known the FDA is a broken agency but did not realize just how badly broken it has become until the Avandia controversy first came to light. Here we are more than two years from the time the Avandia controversy came along with millions spent on research and panel meetings and still no decision from the agency on whether Avandia should be pulled from the market. Although Diabetic Investor is not a big fan of how Avandia’s critics have acted, they have to their credit been very clear from the start that Avandia should not be on the market.


Thankfully physicians have not waited for the agency to act and have taken matters into their own hands switching patients from Avandia to other medications. The only problem with this prudent approach is the drug many of them used to replace Avandia, Actos is now under attack. So once again they must now tell their patients a drug they once thought to be safe is no longer safe and it’s time once again to move to yet another medication. Is it any wonder that therapy non-compliance, already an issue before the Avandia controversy, is a bigger problem than ever?


This also presents an interesting dilemma for physicians with new medications such as Victoza® from Novo Nordisk (NYSE:NVO) and Bydureon from Amylin (NASDAQ:AMLN), Lilly (NYSE:LLY) and Alkermes (NASDAQ:ALKS). Both drugs offer solid glucose control, ease of administration, the potential for weight loss and neither appear to have any major adverse cardiovascular events and actually appear to have cardiovascular benefits. Even though Bydureon is an extension of Byetta, a drug used by millions, physicians must still be weary of possible unknown side effects from long term usage. As we have seen clearly with Avandia and Actos, no one knows with any certainty what adverse events will appear years down the road. Diabetes is a chronic disease which means that patients will be taking these drugs for the rest of their lives. While drugs like Victoza and Bydureon look great today it would not be unreasonable for a physician or patient to wonder what adverse effects, if any, might come along five or ten years from now.


The FDA has actually made this dilemma even worse as they have become obsessed with events rather than science. A perfect example of this is when the agency issued a notice on Byetta and pancreatitis. Rather than investigate this issue and conduct some actual research in a rush to judgment the agency issued a letter notify physicians about a “possible” link between Byetta usage and pancreatitis. Never mind that the actual incidence rate was actually lower for Byetta users than patients using other medications or that patients with diabetes have a higher incidence of pancreatitis, the agency went ahead with an ill-advised letter which did little more than hurt Byetta sales and scare physicians and patients.


The unfortunate reality is the FDA has lost all perspective and balance when it comes to diabetes drugs and adverse events. Diabetes is growing at epidemic rates and has become not just a healthcare but economic crisis. It’s also a fact that nearly two-thirds of all patients are not properly controlling their diabetes. Finally it’s also a fact that patients with diabetes are at an increased risk for several co-morbidities. Rather than understand and accept these facts, the FDA seems to believe that if just one patient experiences an adverse event the medication they use should be investigated.


One just might think that someone at the agency would understand the concept of risk/reward analysis. Or that someone would look at real scientific evidence rather than accept without question data from the suspect math of a meta-analysis. Perhaps it’s just too much effort to actually speak with the experts and understand that diabetes is the true enemy and the risk of poor controlled diabetes outweighs the possibility that a drug MAY be linked with adverse events. Under the convoluted logic used by the agency it’s better to act first and investigate later.


Diabetic Investor understands it’s not easy to accept the fact that some patients will experience adverse events from the drugs they use to fight diabetes. However in any war rule number one is fine and brave soldiers will die and rule number two is there is nothing anyone can do to change rule number one. This is the nature of war.


The same concept applies to fighting diabetes. While the FDA should do everything possible to limit adverse events, they must also balance this concern against the numerous casualties caused by poorly controlled diabetes. By their actions the FDA appears to be living under the delusion that there is such a thing as an adverse event free drug. This is not just foolish but dangerous as well.


Looking at the actions of the FDA, Diabetic Investor can understand why so many people are fed up with what’s going on in our nation’s capital. Based on their actions the bureaucrats in Washington have lost all semblance of what’s going on in the real world. While Diabetic Investor does not necessarily believe TZD’s should be pulled from the market, this action would at minimum allow patients and physicians to move on.


Since the Avandia controversy started Diabetic Investor has looked at the situation through a rather simple premise; will any good come from it. Will new drugs be safer? Will physicians be able to answer a simple question they hear from patients almost every day- Is the medication I’m taking safe? Will drug companies understand clearly what the agency wants? And ultimately will we see any improvement in patient outcomes? Sadly the answers to all of these questions are a resounding NO.


The fact is the FDA, an agency that is supposed to protect the public, is doing the exact opposite. One has to wonder how many patients will needlessly suffer because the FDA lacked the stones to make a decision.