FDA to review Enhance study

Two weeks into the Vytorin saga, the daily dose of news has grown into a gout. Here's a summary:

U.S. drug watchdogs will review the Enhance study, which showed Vytorin--a combo of Zetia and Zocor--didn't affect arterial plaque any more than Zocor did alone, despite the fact that the combo did a better job a lowering "bad" LDL cholesterol. A report is expected in eight months. Okay, fine. The kicker? FDA also plans to consider whether it should change its approach to cholesterol-lowering drugs. Now, those drugs are typically cleared for market if trials show they cut LDL. If the FDA started requiring patient outcomes--such as fewer heart attacks or reduction in arterial plaque--the pharma industry might have a stroke.

After dissecting Merck and Schering-Plough's defense of Vytorin--which included a pages-long timeline of Enhance-trial decisions--experts and analysts still weren't appeased. Among the questions: Just what makes data "biologically implausible?" Because we aren't scientists, we have our own question. The timeline says the data wasn't "unblinded" until Dec. 31, meaning that no one knew which group of patients got which therapy. That's key but even then, wouldn't it have been obvious that the two groups' results were essentially the same? It doesn't matter which group is which if the problem is that neither was better. We'd love to be enlightened on this point.

New York Attorney General Andrew Cuomo has joined the queue of investigators scrutinizing the Enhance study. Cuomo subpoenaed Merck and Schering-Plough as part of a probe into whether they "deliberately concealed" the study's negative results and into the "aggressive marketing" of Vytorin in the meantime. The AG also is looking into Schering execs' stock sales after the study wrapped but before the results went public.

Forbes reviews the performance of Schering CEO Fred Hassan, previously hailed for his turnaround of that company, now under fire for his role in the Enhance study. Forbes's take? Hassan "botched it," and his "excuses are thin." To be fair, we have to refer to a letter Schering-Plough sent to Forbes in response; asking for a handful of corrections to the piece, the letter defended Hassan and Schering's actions.

The American College of Cardiology issued a new statement about the Enhance trial, saying that its first word on the subject [1] wasn't meant to imply an endorsement of Zetia, one component of the Vytorin combo treatment. You'll recall that soon after the trial's results were made public, ACC urged patients not to rush to judgment. Since then, two Congressional committees roped the doctors' group into their investigations of the trial.

- read the FDA's announcement [2] of its study review
- here's Merck/Schering-Plough's Enhance response and timeline [3] (.pdf)
- read the FDA review report [4] from the Boston Globe
- see Forbes' timeline coverage [5]
- read about the New York AG's investigation [6] in the Wall Street Journal
- get Forbes' report [7] on Hassan; see Schering's letter [8] in response (in the comments section)
- read about the ACC's new statement [9] at Pharmalot

Related Articles:
Merck, Schering defend embattled Vytorin. Report [10]
Vytorin defenders funded by drugmakers. Report [11]
Vytorin, Zetia scrips plummet. Report [12]
Vytorin spots "shame" the ad industry. Report [13]
Congress promises Vytorin hearings. Report [14]
Merck, Schering's Vytorin fails trial. Report [15]