At first glance, Merck's Cordaptive is yet another combination drug for cholesterol. But by unlocking the significant medical benefits of niacin, the treatment may represent an important advance. Cordaptive contains an anti-flushing agent which reduces the key side-effect preventing wider niacin use.

In early January, Genzyme nabbed one of the highest-value specialist cholesterol-busting drugs around: Phase III mipomersen, from Isis Pharmaceuticals. But given the ENHANCE-triggered questions around the value of ever-lower LDL, it's reasonable to ask whether mipomersen has a somewhat less rosy prospect in the few weeks since the deal was signed.

Not quite three weeks after triggering a medico-commercial earthquake with the ENHANCE trial results, Schering-Plough and Merck have yet to win back three key constituencies: prescribers, patients and investors. The stakes for not doing so are enormous. But more importantly for the industry as a whole, ENHANCE is the latest and strongest sign that the cornerstone on which blockbuster franchises are built-simple, compelling and easy-to-verify measures of treatment success--is crumbling in the face of biological complexity. And that means that primary-care success is going to get a lot more expensive.