What do you get when you combine a trial design that failed to show improved patient outcomes, two cholesterol-lowering drugs, and an FDA not-approvable letter? A clinical trial destined for cancellation.
Merck (NYSE: MRK ) announced yesterday that it was cancelling its ACHIEVE (An Assessment of Coronary Health Using an Intima-Media Thickness Endpoint for Vascular Effects) clinical trial, after the study showed every sign of flopping badly.
ACHIEVE was testing MK-0524A -- formerly called Cordaptive, before the FDA nixed that name. The drug combines Merck's extended-release niacin with laropiprant, a novel flushing pathway inhibitor. The combo drug lowers bad cholesterol and raises good cholesterol without creating the flushed feeling that regular niacin causes in patients.
Like the Enhance trial, which tested its already-approved drug Vytorin, ACHIEVE was measuring the thickness of an artery to show that the drug could decrease the plaque buildup that leads to heart attacks and other ailments. Unfortunately, the patient population used in both the Enhance and ACHIEVE trials -- people with high cholesterol because of an inherited mutation -- are being treated much better today before entering the trial, compared to when a similarly designed trial for Pfizer's (NYSE: PFE ) Lipitor succeeded. A lack of improvement on a "healthier" population looks considerably worse than Lipitor's improvement on a "less healthy" one did.
However, Merck and Schering-Plough (NYSE: SGP ) argue that there is so little plaque in the arteries of the patients when they enter the trial that it's difficult to show an effect from cholesterol-lowering drugs.
Merck hasn't said why the FDA rejected MK-0524A. It's possible that the agency may require all companies to run a study showing that a cholesterol-lowering drug reduces the rate of cardiac events, such as heart attacks and other complications, before it will approve the drug for less needy patients. This seems to be the case for Isis Pharmaceuticals' (Nasdaq: ISIS ) and Genzyme's (Nasdaq: GENZ ) mipomersen. Along these lines, Merck has started a trial measuring cardiac events, but the results aren't expected until 2013.
Of course, it could be some minor factor keeping Merck from getting the agency's green light for MK-0524A. We just don't know yet.
In any event,competitors with cholesterol-lowering drugs already on the market, like AstraZeneca's (NYSE: AZN ) Crestor and Abbott Labs' (NYSE: ABT ) Niaspan, will get more time to enjoy the Enhance-d problems Merck has managed to ACHIEVE.