Whitehouse Station: "Let's Regain Control Of The Cholesterol Narrative" -- Fail

UPDATED: 11.15.09 @ 9:30 AM EST -- Merck's Dr. Pasternak used to sing a very different tune, apparently, back when Merck was seeking approval of Cordaptive, a niacin-added cholesterol management combo pill -- subsequently rejected by FDA. [Tremendous thanks go to an anonymous commenter, below.]

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With this extraordinary Saturday press release, and a "preprint" of a letter sent to The New York Times by Dr. Dick Pasternak, Vice President of Clinical Research (excerpted below), New Merck is trying to get out ahead of the likely avalanche of stories on Monday morning:

Letter to the Editor
The New York Times
620 Eighth Avenue
New York, NY 10018

To the Editor:

The New York Times story today about a clinical study called ARBITER-6 misses two key points that we believe your readers should know.

First, the results of ARBITER-6 have been described by others as largely predictable, as an analyst quoted in your story notes. But that is not because one drug is necessarily better than the other. Patients in ARBITER-6 were extensively pre-treated with statins, and had well controlled LDL but relatively low HDL, which is a study design that strongly favors a drug with niacin's effects on HDL over an LDL-focused medicine such as ezetimibe.

Second, because ARBITER-6 did not include a true control group, absolute benefit for either medicine in this study cannot be determined. The lack of a control arm, as well as the statin pre-treated patient population, should lead one to be extremely cautious in the interpretation of the results of this small study. . . .

What all of this -- out of Whitehouse Station -- fails to address, however, is that if Arbiter 6 (before it was stopped), in fact did show benefits of Niaspan over Zetia, that will be three straight studies in which no positive outcome was seen for employing Zetia or Vytorin.

And that "strike-out, on three consecutive pitched balls" will stand in stark contrast to the impressive outcome studies showing the benefits of Crestor (in JUPITER) specifically, and of statins generally -- in literally dozens of studies going back more than a decade. Studies that show a reduction in risk of cardiovascular events from statins -- and of course, diet and exercise, first.

The tempest of Arbiter 6 is not the crux of it -- no, the crux of the story on Monday ought to be the dearth of data showing any benefit for Vytorin/Zetia -- despite cumulative global sales of these two drugs since 2003 (through the first nine months of 2009) of over $20 billion (as calculated by tallying the companies' SEC Form 10-K and 10-Q filings from 2003 through 2009).

$20 billion -- and there is no proof that these drugs improve outcomes. I think I read that Old Schering-Plough/Merck joint venture spent about $470 million (per TNS Media Intelligence) on TV DTC and other direct advertising for Vytorin and Zetia from 2006 to 2008, alone. At a bare minimum, we ought to be disappointed in that waste of resources.

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[From the anonymous commenter, below:]
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. . . .Interesting tune from Dick, and one that is very different from the past when Merck was trying to get FDA approval of Cordaptive (epic fail!):

". . . .If approved, Cordaptive could be used by patients who cannot take statins or those who already take statins but need to further improve their cholesterol levels, Richard Pasternak, Merck's vice president of cardiovascular disease research, told Dow Jones Newswires." (Sept 4, 2007)

"I realized HDL has become tarnished because of torcetrapib, but Cordaptive uses a completely different mechanism," Pasternak said. "In my mind at least, this does not tarnish the tremendous body of evidence that HDL is protective and low HDL is associated with clinical risk." (Sept 2, 2007)

"Dr. Richard Pasternak, a senior Merck research official who helped conduct the trial, said the findings could trigger a rethink of treatment strategies.

"It's a breakthrough because this comprehensive lipid therapy has not been available or achievable by most people. Physicians are reluctant to prescribe the agent (niacin) and patients are reluctant to take it," he said in an interview." (Sept 2, 2007)

"So I would think most people, excuse me, in this room are aware of the magnitude of the problem that we face with respect to cardiovascular disease in general and specifically dyslipidemia, while most people think about dyslipidemia in the context of an elevated LDL, it's quite clear that other key lipid parameters, particularly HDL and to a certain extent triglycerides represent a therapeutic challenge and an unmet medical opportunity to improve the cardiovascular health, and Cordaptive in particular is an agent that is targeted to address all three key lipid parameters. Recall that as terrific as statins have been, and I used to be out as an academic cardiologist on the lecture circuit talking about what remarkable improvement in mortality and morbidity that it brought us but I think as we look back at that we have to recognize that the cup was only one-third full, or two-thirds empty, because statins only reduce mortality and morbidity only by 30 or 40%, so there is a tremendous burden that continues to exist and continues to search for treatment alternatives.

Niacin has been known for 50 years to have favorable lipid effects but despite these favorable lipid effects it's been a challenge to get people to take Niacin on a regular basis no matter what form it's come in, so despite these well known, well established favorable benefits both in terms of the lipids as I just mentioned but in terms of fairly robust outcomes over decades, the majority of patients who take Niacin experience flushing with Niacin." (March 18, 2008)

[Posted by Anonymous, on] November 15, 2009 7:43 AM. . . .

A sincere debt of gratitude is owed to this anonymous commenter. Later today (Sunday brunch calls!), I'll go get links to each of these statements, above -- if they are available somewhere online.

Funny how Dr. Pasternak's tune changes, depending on what agenda (niacin "breakthrough": 2007-2008; niacin not so important: November 2009) he's pushing, at any given moment.