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Merck hits a bloop single in an epic PhIII CETP cardio contest. Now what?

Merck $MRK has an interesting dilemma on its hands.

The drug’s enormous Phase III study of its CETP drug anacetrapib came through on the key endpoint — but it was at best a base hit for an enormous patient population. And after it missed a key secondary and showed signs of accumulating in fat, Merck now has to decide if it wants to go to bat with regulators in search of an approval for a marginal heart drug.

We already know the top-line score for this longrunning legacy effort. But the details released early Tuesday are devilishly difficult for Merck, which has yet to decide how — or whether — to shoot for an OK after three similar drugs all flopped in their own final clinical showdowns.

The good news:

Across the study population of more than 30,000 patients, the drug arm demonstrated a 9% reduction in the risk of a composite of major coronary events: coronary death, myocardial infarction or coronary re-vascularization. That translates into a lean and hard-to-market 1-point difference — a significant but so-so 10.8% compared to 11.8% — in the rate of events. And it was a consistent result across the sub-groups that the researchers wanted to follow.

After a bit more than 4 years of treatment on average, non-HDL cholesterol level declined by 17 mg/dL; good HDL levels rose by 43 mg/dL.

The bad news:

Dragging behind on expected rates of presumed ischemic stroke, researchers concluded that the drug missed the key secondary endpoint of their composite of major atherosclerotic events: myocardial infarction, coronary death or presumed ischemic stroke.

Tellingly, Merck did not bring in the French horns to herald the results. Bottom line:

Merck is reviewing the results of the trial with external experts and will consider whether to file new drug applications with the U.S. Food and Drug Administration (FDA) and other regulatory agencies.

Can you sell a drug like that? Maybe, but not for the big, big money Merck is looking for. Perhaps Merck will wait and see what the KOL community in cardio says about the hard data, and whether this is a drug worth campaigning for.

The early returns don’t look so good, as some of the KOLs noted that the slight benefit from the drug came from the low drop in LDL, rather than the spike in HDL. And there are better ways to cut LDL far more.

Roy Baynes, Merck

Payers have become distinctly rebellious when it comes to the PCSK9 drugs’ $14,000-plus price, unhappy with the lack of a clear mortality benefit that has been giving Amgen fits. They’d likely want a low price for a 1-point improvement on cardio events, which Merck would have to consider before filing for an approval and starting an uphill marketing slog. And company execs are treating this rare and unexpected win with kid gloves.

“We are pleased that adding anacetrapib to statin therapy resulted in a further reduction of major coronary events in REVEAL,” said Roy Baynes, the CMO at Merck Research Laboratories. “This trial helps to advance our understanding of the effects of anacetrapib on cardiovascular risk, and we are grateful to the study leaders at Oxford, TIMI, the many investigators, and the thousands of patients who participated in this study for their efforts.”

Merck has been making great strides with its PD-1 cancer star Keytruda. But outside of oncology it’s been hit with a series of setbacks and small wins, like this, which few analysts are paying much attention to.



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