Avandia – Will any good come from all this?

Avandia – Will any good come from all this?

Next Tuesday and Wednesday the FDA will be conducting a much anticipated meeting to decide the fate of Avandia. In what will surely be a three ring circus atmosphere the FDA hopes to decide once and for all whether or not Avandia should be pulled from the market. While Diabetic Investor expects little real news to come out of this circus as the Avandia controversy has been debated for over two years now, our thoughts have centered around one key and very critical question; Will any good come from this whole controversy?

Sadly Diabetic Investor expects the answer to be a resounding NO! All too often meetings such as these become a place the blame meeting, rather than let’s try and solve the problem meeting. Diabetic Investor anticipates much pontificating, lots of statistics, some strong opinions on the pro’s and con’s of the use of meta-analysis and lots of rancor about who did what to whom and who ultimately should be blamed for this whole mess. If there is one thing Washington DC is very good at its placing blame after a problem has been identified but not yet solved. Anyone who doubts this only needs to look at the oil spill in the Gulf which continues to flow with no end in sight.

Actually there are several similarities between what’s happening in the Gulf and the Avandia situation. In both situations there is plenty of blame to go around, no one is quite sure of the long term consequences and there is little hope that any long term good will come from the situation. It’s also true that both BP and GlaxoSmithKline (NYSE:GSK) are managing their respective situations more from a legal perspective than what’s actually good for the general public.

There are some who believe that GSK should just pull Avandia from the market and make the best of a bad situation. They could even try and put a positive spin on this by stating that while they believe Avandia to be safe and effective they see the controversy hurting patient care and in it’s in the best of patients to put this situation where it belongs, in the past. Based on interviews with several experienced class action attorney’s Diabetic Investor doesn’t see this as a possibility. According to these interviews the attorneys believe the GSK attorneys are advising the company that any withdrawal of the drug would be tantamount to an admission of guilt and therefore increase their legal liability.

Diabetic Investor has also learned there is a split within the FDA, with one side believing Avandia should be taken off the market and the other believing the evidence presented to date does not warrant a withdrawal. Here is where the debate surrounding the use of meta-analysis comes into play. Diabetic Investor has interviewed several well respected researchers and about the only area where there is universal agreement is that meta-analysis is too subjective of a tool to be reliable in this situation. As one expert stated the results of the meta-analysis vary widely depending which data sets are included or excluded from the analysis.

But the situation becomes even more complex when you consider that patients with diabetes already are at increased risk of adverse cardiovascular events just because they have diabetes. This is not unlike what happened to Byetta and the whole issue over pancreatitis. Diabetic Investor does find it noteworthy that GSK has not followed the same path Amylin (NASDAQ:AMLN) pursued when the pancreatitis issue arose. To help alleviate concerns over this issue Amylin examined insurer’s databases and found the incidence rate of pancreatitis for Byetta users was actually lower than the incidence rate for the general diabetes population. Perhaps GSK felt such an analysis would be inconclusive as there are numerous possible contributing factors for cardiovascular events and therefore they could not conclusively exclude Avandia as a factor.

Given all the moving parts here Diabetic Investor believes the FDA has placed themselves in a no win situation. Should the panel vote for removal of Avandia question will arise as to why the agency did not take action sooner. Additionally many will ask the logical question as to why the agency did not see these issues while the drug was undergoing the approval process. On the flip side should the panel recommend Avandia be allowed to stay on the market, many will ask why the agency wasted the taxpayers time and money on this subject. Worse still would be a split vote leaving the decision up to the FDA, as Diabetic Investor has noted before passing the buck is also another grand Washington tradition. Or put another when the going gets tough, take yourself off the hook and let someone make the tough decisions.

Yet all this merely conjecture and the real question remains; will any good come from all this.

Looking at the question from the perspective of the drug companies the answer is clearly no. The drug approval process, as flawed as it may be, was already a cumbersome and expensive process before the Avandia controversy. Today this process is even more cumbersome and more expensive given the new rules the FDA put in place because of the controversy. As Diabetic Investor has noted on several occasions because of Avandia the FDA has become overly conservative and appears to be looking for reasons NOT to approve new drugs.

Diabetic Investor can think of two clear examples of the collateral damage created by the controversy and both come with GLP-1 drugs. Victoza® from Novo Nordisk (NYSE:NVO) received approval with a black box warning related to thyroid cancer concerns. While Diabetic Investor believes Novo mishandled this issue, the scientific evidence on the subject does not support the need for a black box warning. Yet the FDA being in the ultra-conservative mode decided to take no chances and approved the drug with the black box.

The second victim is Bydureon from Amylin. A drug that frankly should have been approved by its original PUDFA date but because the FDA was so wrapped in Avandia the agency merely issued an approvalable  letter, making patients wait even longer for this game changing drug. Unlike Victoza, Bydureon is basically a line extension of Byetta, a drug that has a long history and is used by over one million patients. Should the FDA approve with the same black box warning as Victoza it would be the biggest crime to hit Washington since Watergate. Like Victoza, there is no scientific evidence to support this, plus the FDA has the additional benefit of reviewing Byetta data which shows no thyroid cancer concerns whatsoever.   

From the perspective of physicians who treat patients with diabetes, the answer to the question is also no. First off Diabetic Investor believes that any physician who continues to prescribe Avandia has completely lost all touch with reality. Not because we believe Avandia is that bad, rather the physician is placing himself at risk of a lawsuit. Add in the fact there are several safe and effective alternatives, it’s amazing there are any patients at all still on the drug.

The legal risk aside, this whole controversy has made the life of these physicians a living hell. How can they honestly answer a patient when the patient asks if the drugs they take every day are safe? Patients do not want to hear that the drugs they take every day “appear to be safe”. They want a simple yes or no. 

Already a conservative group Diabetic Investor can only imagine how physicians will prescribe new and very effective drugs like Victoza and soon Bydureon. Will they become even more cautious preferring to let someone else use their patients as human lab rats? These physicians aren’t stupid they understand firsthand the devastating consequences from poorly controlled diabetes and prior to the Avandia controversy were beginning to move away from the treat to failure approach and where becoming more aggressive treating their patients with diabetes. Worried that new drugs, as good as they look in clinical trials, may latter develop unknown adverse events it’s perfectly understandable they would stick with drugs that proven themselves over the long term even when those drugs might not do the best possible job for the patient.

The biggest NO comes from the perspective of the patient, who once again is the loser here. While all these so-called experts claim to have the best interest of the patient at heart, that’s difficult to swallow given how this situation has impacted real people with diabetes. Studies have shown that patients, many of whom were already non-compliant with their therapy regimen before the controversy, have become even less compliant since the controversy hit the national spotlight. Avandia was not just a very popular drug, for many patients it was very effective.  Understandably these patients, who read newspapers and watch the news, do not want to risk a heart attack so they stopped taking Avandia. Even worse as studies have shown they were reluctant to take the medication their physician prescribed as a replacement for Avandia.

Worse still patients are losing faith in the FDA. While drug companies have never been held in high esteem by the general public, patients used to believe the FDA was there to protect them.  After a series of drug related issues, in the eyes of the general public the FDA is more like the Keystone Cops than an agency that can protect the public.

In the real world, somewhere where the FDA and many of these so-called experts do not live, people understand that there is no such thing as a completely risk free drug. They understand a simple concept which appears beyond the FDA called risk/reward analysis. What patients and the physicians that treat them really want is an honest assessment of what the true risks are balanced against the possible rewards. Or put simply they want to make an informed decision about the drugs they will take for the rest of their lives.

Here we are two years after this whole mess started and there is no clear consensus from these so-called experts as to whether or not Avandia does or does not increase adverse cardiovascular events. For every expert who is adamant that Avandia increases cardiovascular risk, there is another who will state the exact opposite. Truth be told, the Avandia controversy has accomplished one thing very clearly, everyone involved with it shares equally in the blame game; a game that has no winners and from Diabetic Investor’s prescriptive far too many losers.