As part of its ongoing investigation into the Vytorin controversy, the Senate Finance Committee is disclosing angry notes written by John Kastelein, who was the primary investigator for the Enhance trial, which found the cholesterol pill was something of a dud. The costly combination of Merck's Zocor and Schering-Plough's Zetia failed to show a benefit over the much cheaper Zocor in reducing plaque in the carotid artery, and even showed a statistically insignificant buildup, although it did a better job of lowering LDL in patients with an inherited form of high cholesterol.
In other words, Vytorin may not be of much use as a first or second-line therapy, a fact underscored by several prominent docs when the complete Enhance data was dissected at the American College of Cardiology conference this past weekend. And the drugmakers are under a microscope for the way they handled the data - they delayed releasing the study for nearly two years; never appointed an independent board; briefly changed the primary endpoint without consulting Kastelein, and some Schering-Plough execs sold huge amounts of stock.
And so the Senate Finance Committee is trying to connects various dots, such as contributions made by Merck and Schering-Plough to the ACC, which urged its members not to panic when the drugmakers two months ago issued preliminary data. Since 2003, Merck and its various foundations and divisions have donated almost $5 million to the ACC for conference booths, expo fees, educational seminars, and satellite event fees. Schering-Plough gave $1 million. Their joint venture gave another $5 million.
Then there's Schering-Plough's '49 Plan' to wine and dine docs in hopes of convincing them to prescribe Zetia, on which $3.5 million is being spent and was first reported by Pharmalot. To keep the pressure on, letters were sent today to Merck and Schering-Plough seeking info about payments to docs. Meanwhile, this is an excerpt from Kastelein's e-mails to John Strony, a Schering Plough exec:
"Is it correct that (Schering-Plough) has decided not to present at (the American Heart Association), but to await the two other, completely unvalidated, endpoints, which analysis is going to take us straight into 2008??!!?? If this is true, (Schering-Plough) must have taken this decision without even the semblance of decency to consult me as (primary investigator) of the study. I can tell you that if this is the case, our collaboration is over...This starts smelling like extending the publication for no other (than) political reasons and I cannot live with that."
The next day, Kastelein wrote again to Strony to say that "I have been travelling half the globe in the last 6 months to a number of large and important meetings at the strong wish of Merck to chair them or to present ezetimibe (Vytorin) data. At every single one of them, I was cleared to say that Enhance would be presented at AHA. There is no reason whatsoever to include femorals; you will be seen as a company that tries to hide something and I will be perceived as being in bed with you!"
In a statement, Grassley says that he is "troubled that (Merck/Schering-Plough) may be placing marketing interests above science. For instance, in an M/SP marketing review done just last December, it appears that advancing sales, not science, was the priority. Page eight of the document details messaging adjustments for 2008 such as 'Incorporate lower is better into message flow' and 'incorporate switch message - SNAG (simvastatin not at goal).' Another slide show created by your respective companies last year noted that, 'History has shown that ZETIA is extremely sensitive to promotion, with consistent share growth demonstrated when fully promoted.' "