Tick, Tock, Tick, Tock

Tick, Tock, Tick, Tock

It seems hardly a day has gone by since the FDA meeting on Avandia when some other piece of news comes out and today is no different. According to Reuters report U S officials have stopped enrolling new patients in the TIDE trial. TIDE was originally designed to compare the heart effects of Avandia vs. Actos, a trial widely criticized by many in the diabetes community as they believed based on available data it’s unethical for the trial to continue.


Also in the news today was the transcript of interview given by GlaxoSmithKline (NYSE:GSK) CEO Andrew Witty. According to the transcript:


So you’re telling me that you’ve now drawn a line under litigation risk for GSK?


Well unfortunately, I can never tell you we’ve drawn a line under litigation risk because it is an ever-present threat, particularly if you trade in the United States where litigation unfortunately is a fact of life, in business and in life generally, in the U.S. But what we have been able to do, and we announced it last week, is we’ve been able to bring to a close or progress toward closure a substantial part of our historic litigation burden, and particularly some of the bigger cases, which have been around for a long time. It was important for us to try and bring closure to these things. And I think we’ve been able to do it in a way which does bring certainty for our shareholders and does begin to close off or has already closed off a number of these cases. So I’m quite happy with where we’ve got to and what we were able to announce last week.


If you’re confident about the safety of Avandia, why was it necessary to make this one-off payment to settle the majority of these cases?


Well in any product liability situation, a company has to look at the kind of allegations which have been made and the cost of defence, versus the opportunities to settle. And not unusually, in this situation and in many other situations for us and other companies, we took the view that it was actually in the best interest of the company’s shareholders to go ahead and achieve settlement on terms that we believe were reasonable for the company, rather than to go through very long, protracted and potentially very expensive defence in this particular area.


Now, having said that, very often we might take a different decision and go ahead and really fight it out in the courts for a particular point. But on this particular occasion, we decided this was the best course of action for the company.


And what do you think comes next in the Avandia Adcom? Do you think the FDA will accept the finding of the Adcom?


I don’t know yet what the FDA action will be. We’re waiting to see what they have to say. As you know, of course, they’ve called this advisory board. They, I’m sure, will take the input and advice that they’ve received. And we look forward to working with the agency on whatever next steps they deem necessary.


Diabetic Investor finds Mr. Witty’s last comment particularly interesting as it seems to indicate that like Diabetic Investor he isn’t quite sure the FDA will actually follow the recommendation made by the panel. As Diabetic Investor reported yesterday such a move is very possible given the split inside the FDA and the fact the results of the panel meeting did not come out the way the Anti-Avandia camp wanted.


Looking at Mr. Witty’s comments in their entirety Diabetic Investor continues to believe the company has already made the decision to voluntarily withdraw Avandia from the market. Just as the company waited to settle the Avandia lawsuits, Diabetic Investor believes the company is playing a similar waiting game before they officially announce the withdrawal. Preferring not to ruffle the feathers of the FDA any further and seeking to avoid any additional legal issues, the company will consult with the agency to make sure they don’t steal their thunder. On the one hand GSK does not want to appear as if they are capitulating when all along they have publicly defended Avandia. On the other, the see the handwriting on the wall realizing that should the FDA ignore the panel vote there is the potential for further legal costs. A very delicate balancing act.


No matter what happens, the final chapter of the Avandia saga has yet to be written and the fallout from the controversy will linger for years to come. The fact is it’s become more difficult to get new diabetes drugs through the FDA. The process is taking longer and costing more, yet no one seems to know whether or not we will see safer, more effective drugs as a result.


Seeking to put some perspective to the controversy, Diabetic Investor reviewed our coverage of another diabetes drug that was eventually pulled from the market; Rezulin. Way back in our July/August 1999 issue we wrote; “The buzz on the exhibit-floor about Warner-Lambert’s type 2 drug, Rezulin, focused on whether or not it would be off the market within the next six months or face a slow, agonizing death.” In what has turned out to be an ironic conversation we went on to state; “One physician pointed out that with Rezulin, there are proven adverse side effects that require patients to have their liver enzymes monitored regularly. Further, Avandia costs a dollar less per pill than Rezulin.”


Looking even further back in the archives back in the March/April 1999 issue we wrote; “On March 26, an FDA advisory committee recommended that Rezulin remain on the market.”


People have forgotten that when Avandia first came along it was viewed as a wonder drug that did not carry any liver risk, the big issue at the time. Back then, as today, many physicians were bombarded with calls from patients asking the same question they are asking today; “Is the medication I’m taking safe?” Also like Avandia, Rezulin was a blockbuster nearly reaching a billion in sales prior to being pulled, voluntarily, from the market.


It should also be noted that just as Glaxo has come under fire for their behavior with Avandia, Warner-Lambert suffered the same fate as many believed they withheld key data from the FDA. Also like Avandia, there were researchers who were skeptical of Rezulin long before the drug hit the market and whose concerns were largely ignored.


Talk about history repeating itself.


It seems the folks at the FDA learned little from the Rezulin experience, as the similarities with Avandia are scary. Diabetic Investor isn’t really surprised by this, as learning from past mistakes is skill the FDA has yet to acquire. This is what makes the Avandia controversy and the circus surrounding the drug seem like just one huge waste of time and effort. 


Looking back at Rezulin and looking at Avandia today it’s difficult to see any good coming from either situation. More likely, after all the pontificating is over, it will be business as usual at the agency. For the time being cardiovascular adverse events will dominate the approval process, just as the liver enzyme issue dominated after Rezulin. A few years will likely pass by until another blockbuster drug comes under attack for a yet unknown adverse event and the cycle will start all over again.


This situation is summed up best something Georg Hegel wrote back in 1900; “What experience and history teach is this- that peoples and governments never have learned anything from history, or acted on principles deduced from it.”  Or as everyone has heard and many have said; “If we do not learn from history, it’s destine to repeat itself.”