Thursday, November 18, 2010

Yale's Harlan Krumholz Provides Objective, Unbiased Look At Merck's Anacetrapib DEFINE Results

This is perhaps the best, most evenly balanced story I've yet seen on Merck's Anacetrapib DEFINE safety study's results. Credit the Milwaukee-Journal Sentinel's John Fauber, and the Sacramento Bee -- often the most independent news-sources on the planet, for at least the last decade (or so, going back to the early Bush-Cheney I days).

Do go read it all, but while the Merck study results presented at AHA yesterday are moderately encouraging, they are far from a knockout -- or even a credible basis for an FDA submission -- and Dr. Krumholz is unafraid to say so:

. . . .Anacetrapib increased HDL cholesterol by an unprecedented 138 percent, while also reducing LDL cholesterol by 40 percent - and that was in people already on cholesterol medication. The study was published online in the New England Journal of Medicine.

"We need to know more," said Harlan Krumholz, a cardiologist with Yale School of Medicine. "They are not going to get approval based on the lab results. It could also cause harm. . . ."

The anacetrapib trial was funded by Merck, and eight of the 12 authors of the study were Merck employees.

Yale Mitchel, Merck's vice president for cardiovascular disease research, said the company is on record as saying it would not seek FDA approval for anacetrapib before 2015.

But he would not directly answer whether there were circumstances in which it would seek to get the drug on the market before then. . . .

Kooroush Saeian, a cardiologist with Waukesha (Wis.) Memorial Hospital, said a new drug that raises HDL and reduces heart attacks would be revolutionary.

But, he added, "As physicians so many times we've been sold a drug and then have gotten burned. . . ."

Indeed. [Dr. Saeian is almost certainly referring to Schering-Plough/Merck's Vytorin®, and the ENHANCE study.]

On that score, Yale's Dr. Krumholz was among the first, and most vocal cardiologists to pull out the yellow caution flags on another Merck would-be cholesterol wonder drug -- Vytorin®, in mid-2008. It is still unclear whether Vytorin is anything more than a very expensive placebo, and we won't know the results of IMPROVE-IT (that drug's larger outcomes study) until 2014, or beyond -- at least a full eight years after it was begun.

We should credit Dr. Krumholz, and Dr. Steve Nissen, at the Cleveland Clinic, among others with making the case -- with being the early voices of reason, out in the pharma cholesterol-management marketing hype wilderness, all while Schering-Plough and Merck were selling billions of dollars worth of a drug that no one could say for certain would work. Neither of them are anti-new drugs; they are both just pro-evidence-based medicine. To this day, it looks like generic statins are far more effective, and at one fiftieth to one one-hundredth the cost of Vytorin.

In the middle of the above article, a Merck research executive refused to rule out seeking FDA approval before the actual outcomes-benefits of Anacetrapib are known.

As a nation, we should cry foul, should Merck attempt a "Vytorin 2.0 strategy," here. After all, close to 40 percent of all the money spent on Vytorin (and presumably Anacetrapib) comes straight from the taxpayers -- through Medicare and Medicaid. We will, of course, keep an eye on this.

Kudos to Dr. Krumholz.


Anonymous said...

OMG. F'ing Merck. Show me the clinical trial and shut up until then. Show me patients don't die from either intended or unintended events (a la torcetrapib). Show me it matters pound for pound like other drugs to use a CETP inhibitor. Start a placebo controlled trial. Start a head tohead trial. Stop asking us to walk through the fun house of Merck drug development full of distorted mirrors. I'm sorry but torcetrapib beat the stuffing out of HDL and LDL too. So, keep it in your pants, and see you in 6 years.

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