After Eli Lilly flop, Merck adds a futility challenge to huge PhIII anacetrapib study

By John Carroll and Tracy Staton

Merck R&D chief Roger Perlmutter

Now that the theory of CETP inhibition has failed three giant late-stage tests, Merck ($MRK) says it will soldier on with one final, huge push for its cholesterol drug anacetrapib. But it's adding in a futility analysis, due by the end of the year, which could force a quick exit. And execs are clearly backing away from their earlier, and much more bullish, expectations.

Storm clouds have been gathering over the CETP theory for years now, as Eli Lilly ($LLY) and Merck persevered in the field even after Roche ($RHHBY) and Pfizer ($PFE) were forced to call it quits with rival programs. Lilly finally conceded just days ago that its effort flopped, unable to live up to its boast that it would triumph in the wake of major failures. Amgen ($AMGN), meanwhile, has jumped in, buying out Dezima in a $1.55 billion deal that adds a CETP follow-up program to its newly approved PCSK9 drug.

Discussing the anacetrapib program during Merck's Q3 call with analysts, R&D chief Roger Perlmutter asserted that the recent failure of Eli Lilly's CETP inhibitor evacetrapib "increases the importance of our own outcomes study."

Merck's IMPROVE-IT study showed that reducing serum LDL cholesterol, not just with statin drugs but with the different mechanism employed by Zetia (ezetamibe), could reduce cardiovascular risks, Perlmutter told analysts. Since CETP reduces serum cholesterol, it's important to know more about the biochemical effects, and REVEAL--with 30,000 patients enrolled--is powered to do that.

The steering committee for anacetrapib, though, had asked regulators to change the REVEAL study's primary endpoint to include ischemic stroke, rather than revascularization, in its composite endpoint, because stroke is a more easily adjudicated result, Perlmutter said, but the FDA preferred the original set-up.

If the steering committee decides the study is futile, Merck will announce that; if not, it will announce that the study will continue. But Perlmutter cautioned analysts not to "over-interpret" such an announcement, because continuing the study won't necessarily mean that anacitrapib is working, only that it's not futile.

"It's important to include this analysis because we don't want to expose people if there's no use," Perlmutter said.

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