How Vytorin Fell Short

Vytorin soon became the leading "switch brand" in the market. More than half of its users abandoned other treatments in favor of the single-pill alternative.

A massive study, known as IMPROVE-IT, should help prove whether patients should have made that change. But results from that 10,000-patient trial will not emerge for years. In contrast, ENHANCE concluded in April of 2006.

Skip Irvine, director of communications for the joint venture, insists that neither company received any clues about ENHANCE until earlier this month. But skeptics, pointing to stock sales by Schering-Plough insiders, have some doubts.

Schering-Plough didn't respond to questions about its insider sales.

In May of 2006, just one month after ENHANCE came to an end, Carrie Cox, president of Schering-Plough's global pharmaceutical business, sold nearly $1 million worth of company stock. Cox would go on to execute even larger sales, clearing more than $5 million on two separate occasions, a year down the road.

Meanwhile, Schering-Plough's top executive had secured $2 million in a stock sale of his own. Hassan pocketed that money at the end of 2006, even as the company wrapped up a banner year that ensured tremendous bonuses.

Industry Setbacks

Still, 2006 brought a blow to the industry as a whole.

Late that year, Pfizer pulled the plug on a new cholesterol treatment of its own. That drug, meant to complement Lipitor, was designed to increase "good" HDL cholesterol and lower the risk of heart attacks. But it led to unexpected deaths, raising questions about next-generation cholesterol drugs overall.

After that setback, Wall Street experts began to raise questions about ENHANCE on a regular basis.

"I must admit, I'm a bit concerned about this trial because you've set up an admittedly medically important endpoint but a challenging design and endpoint" all the same, Cowen analyst Steve Scala said during Schering-Plough's fourth-quarter conference call in January of 2007. "AstraZeneca's (AZN Quote) METEOR trial of Crestor, I believe, will report at around the same time, and its endpoint is likely much more achievable.

"So from a marketing standpoint, how would you deal with a situation where METEOR is successful but ENHANCE is not?"

Schering-Plough responded in a manner that would soon become routine. The company emphasized the complex nature of the specialized trial -- focused outside the mainstream population -- and warned that the results would take some time.

"We're in no rush to get a marketing thing out of this," Hassan assured.

Unlike Schering-Plough, The New York Times has since noted, AstraZeneca took just 10 months to report favorable results from its cholesterol drug trial.

Mounting Concerns

Meanwhile, quarter after quarter, analysts kept asking Schering-Plough about ENHANCE. In response, Schering-Plough began downplaying the significance of that trial -- insisting that the value of lower LDL had already been proven -- and directing attention to the ongoing IMPROVE-IT instead.

Finally, in mid-December, Congress began demanding answers as well. And as the new year began, Schering-Plough found itself peppered with ENHANCE-related questions at a presentation hosted by Morgan Stanley.

In fact, that "CEO Unplugged" conference, with its question-and-answer format, brought ENHANCE to the forefront like never before.

"So let me just cut to the chase," Morgan Stanley analyst Jami Rubin began in one address. "What's the organization thinking embarking on this study and putting such an important franchise at risk given that you didn't have to do the study?

"But now you own the study, and it's yours, and you've got to continue to protect what is obviously the most important franchise" for the company.