Are We About To Witness A "Revival" Of the CETP Inhibitor Class -- As Genomics Tailored Heart Medications?

So, back in mid-January 2015, the ever-perceptive and savvy pharma-writer John Carroll, over at FierceBiotech, noted that this once hailed, then derided class of purported cholesterol medicine candidates might make a comeback, of sorts. Or, at least, Roche's version might -- as a targeted therapy for patients with the right genetics. So, Roche is potentially rethinking dalcetrapib, as a "personal genomics" driven cardio-protector? That's pretty. . . unusual, to say the least -- given the very rocky road the CETP class has traveled (and slid head-long off the side of the mountain, actually), in larger studies (and recall Pfizer's much-earlier flame-out).

And now, just a few hours ago, John LaMattina, a Merck alum writing at Forbes, has highlighted Roger Perlmutter's emerging view -- that Merck's ongoing large (30,000 patient) CETP candidate study will read out in late 2017/early 2018 with an actual edge -- driven by lowered LDL (i.e., not the mechanism expected). Either way, Merck will have easily spent $500 million on the study. And in a class where Pfizer saw increased mortality in the early part of the last decade. Upshot? This game is decidedly not for "the faint of. . ." um. . . heart. Rim-shot. I think, just like with IMPROVE-IT, the effect will be only slight improvement -- and may not translate to in-office visit benefits sufficient to justify the perhaps 100 fold price multiple, over generic statins. But we shall see.

So, back to John Carroll's Roche musings, then -- about personal genomics, and Roche's dalcetrapib (nice twist!):

. . . .Back in the spring of 2012, Roche was forced to scrap its closely watched cholesterol drug dalcetrapib, a bitter setback that forced the company to start re-evaluating the entire R&D process while raising questions about the entire class. But now scientists in Canada say they have drilled down into the massive data files from the development effort and found that a subset of patients with the right genetic profile benefited greatly from the drug. They've published their results in Circulation: Cardiovascular Genetics. And now they plan to follow up with a new study in an effort to revive the long-dead drug. "These results will lead to a genetics-guided clinical study in patients with the appropriate genetic background to allow review by health regulatory agencies and to provide personalized therapy with dalcetrapib. . . .

As I wrote in 2010, Merck's Anacetrapib had shown (at least at that stage of the game) considerably better lab results than Roche had, with its CETP candidate. There is no suggestion, however, yet -- that the enhanced genomics-differentiated effectiveness will appear in Merck's study results. Wow. So, even if this all pans out, both Roche and Merck will face a population -- by 2018 -- that has been on statins (at perhaps one-one hundredth the price) for seven to ten years, and is seeing real benefit from that course of therapy. It is not at all clear (except perhaps in the sub-class of patients with perfectly matched genomics), why a doctor would be willing to switch his or her patient to this undoubtedly much, much more expensive alternative.

But here's to hoping -- hoping that Dr. Perlmutter is right, and I am wrong. Or, as Mr. LaMattina has put it: ". . .Merck is not putting any credence in the potential for the HDL elevating properties of anacetrapib for reducing cardiovascular risk. They are resting all their hopes on the enhanced LDL cholesterol lowering capacity of anacetrapib which, when combined with a statin, is superior to a statin alone. Who would have ever thought that a CETP program would be viewed as an LDL lowering approach?. . . ."

Indeed, who? I must confess, all of this does feel just a bit like an episode from the later seasons of The Walking Dead. Just rehashing the mayhem, perhaps. . . but I do like the idea of a genomics-tailored approach to heart medications. I wonder how many patients will potentially fit dalcetrapib's genetic marker profile(?). Will it be in the low thousands, or the low millions? Or somewhere in between? We shall see, in time. In time. . .