Analysts, experts write off Merck's huge anacetrapib PhIII

Cleveland Clinic's Steven Nissen

Three years ago, Eli Lilly ($LLY) heart specialist Jeffrey Riesmeyer scoffed at the notion that the failure of CETP inhibitors at Roche ($RHHBY) and Pfizer ($PFE) was a bad sign for their big Phase III program for evacetrapib. 

"What you have here is a weak inhibitor of CETP," he told Bloomberg in 2012. Lilly's evacetrapib, he maintained, would prove that a stronger inhibitor could succeed in managing cholesterol and preventing heart disease.

Evacetrapib wound up proving that Lilly was dead wrong about its theory. And now analysts and experts are either writing off the last remaining CETP inhibitor at Merck ($MRK), anacetrapib, or relegating it to a wild card position on the sidelines of drug development.

"The fact that the trial was terminated due to futility in CV risk reduction casts a deep shadow over MRK's (MP) CETP inhibitor, anacetrapib, currently in Ph3 CV outcome study (the REVEAL trial)," noted Leerink's Seamus Fernandez.

"In baseball you don't get four strikes," the Cleveland Clinic's Steve Nissen told Reuters about the prospects for Merck's candidate.

The failure of three straight CETP drugs, though, has further boosted the prospects of two newly approved PCSK9 drugs. And even the early clinical disasters weren't enough to stop new deals in the CETP field. Amgen recently inked a $1.5 billion deal to acquire Dezima, which has been working on an oral CETP drug.

Merck has made a major comeback with its PD-1 drug Keytruda, but with an earlier consensus of $1.2 billion in peak sales forecast for anacetrapib, Merck is still betting big on the outcome of its huge, 30,000-patient study for anacetrapib. Data are due in 2017. And even after acknowledging the bleak prospects, there's still a case to be made for a potential success.

Does the evacetrapib failure "nail the coffin lid closed on CETP inhibitors?" asks Bernstein's Timothy Anderson. "The reflexive answer is 'yes,' but another possibility is that ACCELERATE was an underpowered study. MRK's REVEAL trial with anacetrapib is ~3X larger than LLY's (30k patients vs 12k), but this partly because slightly different patient populations are being studied.  LLY's trial was in a 'sicker' cardiovascular population, where cardiovascular events in theory would accrue at a higher rate, whereas MRK's trial is in less sick patients. The much larger size of MRK's trial leaves open the possibility that MRK's drug could still prevail. Final results are due in early 2017, but it is possible that interim analyses along the way could yield information earlier than this. Investors will now assume futility with anacetrapib, but even before the LLY news, expectations on MRK's program have been quite low because of the drug's unusually long half-life. From here, anacetrapib becomes a 'freebie' if it were to work. If REVEAL is successful, they now have one less competitor to worry about."

- here's the Reuters story

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