Hoffman La-Roche's Dalcetrapib Is About Two Years Ahead Of Merck's CETP Inhibitor

Despite all of this past week's Merck-generated hoopla (or perhaps because of it), some quiet truths remain -- regardless of whether anyone in the main stream science media repeats them.

First, Pfizer's deadly flame-out with torcetrapib (in this class) back in 2006 should make all responsible scientists quite circumspect about unwarranted claims -- claims without solid outcomes evidence.

Next, rather quietly, back in July of 2009, Roche began a 15,600 patient Phase III, multi-center efficacy/CV outcomes study on its CETP inhibitor candidate, called Dalcetrapib. Merck will take the equivalent step, with its CETP candidate, Anacetrapib, on its timeline, sometime in early 2011, in a 30,000 patient trial run by Oxford University, to be called REVEAL.

Thus, Merck is now -- simply stated -- a couple of years behind Roche -- but Merck's Anacetrapib is showing (at least at this stage of the game) considerably better lab results, with its CETP inhibitor candidate. From a July 2009 abstract (published in the American Heart Journal) describing Roche's 15,600 patient study -- called "dal-OUTCOMES", then:

. . . .Despite contemporary therapies for acute coronary syndrome (ACS), morbidity and mortality remain high. Low levels of high-density lipoprotein (HDL) cholesterol are common among patients with ACS and may contribute to ongoing risk. Strategies that raise levels of HDL cholesterol, such as inhibition of cholesterol ester transfer protein (CETP), might reduce risk after ACS. Dal-OUTCOMES is a multicenter, randomized, double-blind, placebo-controlled trial designed to test the hypothesis that CETP inhibition with dalcetrapib reduces cardiovascular morbidity and mortality in patients with recent ACS. . . .

The study will randomize approximately 15,600 patients to receive daily doses of dalcetrapib 600 mg or matching placebo, beginning 4 to 12 weeks after an index ACS event. There are no prespecified boundaries for HDL cholesterol levels at entry. Other elements of care, including management of low-density lipoprotein cholesterol, are to follow best evidence-based practice. The primary efficacy measure is time to first occurrence of coronary heart disease death, nonfatal acute myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, or atherothrombotic stroke. The trial will continue until 1,600 primary end point events have occurred, all evaluable subjects have been followed for at least 2 years, and 80% of evaluable subjects have been followed for at least 2.5 years. . . .

Dal-OUTCOMES will determine whether CETP inhibition with dalcetrapib, added to current evidence-based care, reduces cardiovascular morbidity and mortality after ACS. . . .

Do stay tuned -- this one is shaping up to play out much like the next-gen Hep C horse-race (between J&J/Vertex's Telaprevir and legacy Schering-Plough cum New Merck's Boceprevir), only at about ten times' the stakes -- and something like 2015 through 2019 finish-line crossings.