Pop quiz: Which one of these drug companies released major positive clinical trial data yesterday?


Intraday Increase Monday from Friday's Close

Merck (NYSE:MRK)


Regeneron Pharmaceuticals (NASDAQ:REGN)


Esperion Therapeutics (NASDAQ:ESPR)


Source: Yahoo! Finance

By investors' reactions, you'd think it was Esperion Therapeutics or maybe Regeneron Pharmaceuticals, but instead it was Merck that finally released data from its IMPROVE-IT clinical trial comparing Merck's Vytorin to Zocor. Vytorin is a combination of Zetia and Zocor, both Merck's, so you can also think of the trial as testing whether adding Zetia to Zocor improves clinical outcomes.

IMPROVE-IT met its primary endpoint of reducing cardiovascular events with Vytorin reducing the cardiovascular risk by 6.4% as compared to Zocor alone. The modest effect partially explains why Merck hardly moved on the news. And, of course, Vytorin and Zetia combined made up less than 10% of Merck's third quarter sales; Merck isn't completely dependent on the franchise.

Unlike these biotechs
Esperion Therapeutics doesn't have any drugs on the market yet. The company has run a couple of successful phase 2 trials on its cholesterol-lowering drug, ETC-1002, and plans to start phase 3 trials next year.

Regeneron Pharmaceuticals isn't as dependent on its cholesterol-lowering PCSK9 inhibitor, alirocumab, since it has a successful blockbuster eye drug, Eylea, but the drug is further along, with plans to submit marketing applications in the U.S. and EU before the end of the year.

Neither company was involved with IMPROVE-IT, but the results of the trial had implications on their abilities to gain FDA approval before cardiovascular outcomes studies are complete.

The Food and Drug Administration has assumed that lowering LDL cholesterol made patients healthier and could be used as a surrogate endpoint for improving cardiovascular outcomes.

But there was worry that IMPROVE-IT might not show an effect because of the modest benefit to LDL cholesterol levels that Zetia adds on top of Zocor.

"Most of the speculation has been that, at best, the study would be neutral. And most -- more than 50% of people -- thought that it was going to be slightly negative," Tim Mayleben, CEO of Esperion, told The Motley Fool in an interview yesterday.

If IMPROVE-IT had turned out how people thought it might, it could have been bad for Esperion, Regeneron, and the rest of the drug companies that are trying to get cholesterol-lowering drugs approved before they complete outcomes studies.

"If it had been negative, then it would have raised additional questions about the LDL cholesterol lowering hypothesis," Mayleben said.

Instead, with positive data, Mayleben said its business as usual: "The word we heard more consistently today -- than perhaps I've ever heard it in my life -- was the word 'reaffirm,' and, that is, that the results from IMPROVE-IT reaffirm the LDL cholesterol lowering hypothesis."

At this point, it seems likely that the FDA will approve alirocumab, which Regeneron is developing with Sanofi. Amgen has a PCSK9 inhibitor evolocumab as well, which will also likely gain FDA approval on or before its target action date of Aug 27, 2015, based on the drug's ability to lower cholesterol.

Ironically, while neither drug will likely need an outcomes study to gain FDA approval, the companies are running them, and the results could ultimately determine which drug wins on the market.