Saturday, May 4, 2013

FDA's Liptruzet® Approval? Yawn. But The "Embedded" FDA Social Policy Question Is Fascinating -- And Unresolved

Let me disclose up front, here that I guess I'm mostly an agnostic -- on the social policy issue presented by yesterday's Liptruzet® approval news. The question, I think is: should it be within FDA's mandate (portfolio of regulatory purview) to deny approval to drugs that -- while not obviously in any way harmful, it would seem -- don't really show an improved survival benefit (or CV risk reduction, in cholesterol management speak). . . especially when (as here) many more effective, and less-expensive offerings are already on-market.

That -- to my mind, at least -- is an extremely interesting (and even post the ACA of 2010, a largely-unresolved) question. As a default "free markets" proponent, I am inclined to say that the market -- essentially, the nation's prescribing doctors -- are so well-versed in the five plus year history of "no improved outcomes" study data for Zetia® plus statin combos, that they are fairly unlikely to load their patients (in any significant way) onto a drug-combo that costs so much more, and lacks actual evidence.

On the other hand, FDA -- at some level -- must realize that (if IMPROVE-IT turns out to show either no-benefit, or a statistically-significant reduction in survival rates) putting even one patient on the combo, precludes that patient from being benefitted by the older -- well-known drugs. So, where is that line crossed, from FDA's perspective? I guess we learned a little more about that -- last night, after the markets closed.

I guess we learned that FDA believes that the nation's doctors, arm-in-arm with the nation's payers (health insurers, and Medicare Medicaid -- and increasingly, the federal and state exchanges, under Obamacare) will sort this out -- in the markets. Pricing, and to a lesser extent, doctors' preferences. That leads directly to what I last wrote on the topic in early January 2013 -- when Merck resumbitted the NDA to FDA, for approval:

". . .And so -- with the Affordable Care Act of 2010 clearly applying new pressures on providers to use the vastly cheaper all-generic equivalents -- who might prescribe this one-off combo drug (especially, at $5.50 a pill)? In addition, given that the massive IMPROVE-IT study isn't likely to answer the question on any CV risk benefit from simvastain plus ezetimibe until late 2014. . . what was the rationale (inside Whitehouse Station) for allocating capital in 2013 to a resumbital of the NDA on the combo (it was dinged the first time, by FDA)?

Perhaps -- just perhaps -- I might answer my own question by suggesting that New Merck had already spent the vast bulk of the money, in 2011 and early 2012, when it made the first NDA submission to FDA. And so, all it was doing was finishing up on the spend -- on the relatively-small chance that the thesis for CV risk reduction via statin-ezetimibe (and therefor, by inference, atorvastatin-ezetimibe) combinations turns out to be supported by actual science, at some future date.

I hope that is the case -- that most of this was long-ago spent money -- sunk costs. And that only a smallish portion (some $5 to $10 million) was needed to get Friday's definitive word back from FDA. . . ."

Finally, here -- from the New York Times -- is MSM's take (do go read it all):
. . . .Although the combination drug, to be called Liptruzet, was shown in a clinical trial to reduce LDL cholesterol more than patients who took Lipitor alone, the company said Liptruzet did not reduce patients’ chances of developing heart disease. That fact troubled some cardiologists, who questioned why it was approved.

“This is extremely surprising and disturbing,” said Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Cardiologists have long questioned the value of Zetia and Vytorin, which combined Zetia with an older statin, Zocor. They had been on the market for a decade, but had not been shown to reduce the risk of heart disease. . . .
Now -- I gather -- FDA has decided: let the markets decide. FDA's stance reflects a view that this debate is outside its central mission, I guess. So, I encourage payers and practicioners to ask lots of questions, before prescribing the combo, or placing it on the upper tiers of reimbursible medicines, for cholesterol management. [This is skepticism I've been repeating since December of 2008 -- and I'm a relative nobody. So others have, and will, certainly follow.]

And with that, I'm out -- to go catch a Derby.

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