Lilly delays its high-risk 'good' cholesterol trial with IMPROVE-IT in mind

Eli Lilly corporate headquarters in Indianapolis

Eli Lilly ($LLY) is extending its massive Phase III trial on a new cardio drug by 6 months in what the company says is a reaction to some recent developments in science. And while the company cautions that its move is not a reflection of the treatment's potential, recent costly failures for similar drugs are sure to spur scrutiny.

Lilly's drug, evacetrapib, is an inhibitor of CETP, a protein that ferries triglycerides between LDL, or "bad," cholesterol and the good variety, HDL. By blocking CETP, evacetrapib is designed to boost HDL levels, and, paired with LDL-lowering statins, the drug can ideally reduce major adverse cardiovascular events (MACE) like heart attack and stroke.

The company's 12,000-patient Phase III trial is designed to determine just that, testing evacetrapib against high-risk atherosclerotic cardiovascular disease. But, after poring over some positive results from a rival drugmaker's trial, Lilly's academic advisers want to give the evacetrapib data more time to mature.

Looking at the results from IMPROVE-IT, an 18,000-patient outcomes trial studying Merck's ($MRK) LDL-lowering Zetia, Lilly's academic executive committee noted that longer exposure to that drug led to less frequent cardio events. And while evacetrapib has a different mechanism of action, Lilly contends that Merck's results have a read-through to its own statin-paired study, called ACCELERATE.

"Many believe, and the academic executive committee and Lilly concur, that these results reinforce the potential for MACE reductions with agents like CETP inhibitors and PCSK9 inhibitors," a Lilly spokesman said in an email. "The decision is not based on any data from ACCELERATE, as both the academic committee and the company remain blinded to efficacy results."

With the delay, an ACCELERATE futility analysis scheduled for this quarter will be pushed back until Q3, and Lilly doesn't expect to notch the trial's final patient visit until July 2016.

Lilly has been working on evacetrapib under the shadow of major late-stage failures from two other CETP blockers, Roche's ($RHHBY) dalcetrapib and Pfizer's ($PFE) torcetrapib. Each showed stellar promise of boosting HDL levels, and each ran into serious safety issues in Phase III that led the two companies to abandon their blockbuster ambitions. But Lilly says those failures have no bearing on their individual prospects. And Merck, which is running a Phase III trial on an anti-CETP medication called anacetrapib, is similarly optimistic.

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