The NYT Put me in Mind of Schering-Plough’s Asenapine, Tonight. . . .

The New York Times today ran a piece on the disappointments encountered by geneticists, recently — in identifying causes of common diseases, through study of the afflicted patients’ genetic code. It truly is a fabulous piece of reporting — do go read it all. I’ll wait.

And so, I was doubly delighted to find that the Times also ran a companion editorial (by Nicholas Wade — do go read it, from top to bottom, as well!), which literally took my breath away, with the grace and precision of its delivery:

. . . .It seems to me the reports represent more of a historic defeat, a Pearl Harbor of schizophrenia research.

The defeat points solely to the daunting nature of the adversary, not to any failing on the part of the researchers, who were using the most advanced tools available. Still, who is helped by dressing up a severely disappointing setback as a “major step forward”?

. . .nature is often a lot more complex than assumed. It now seems that the arm of natural selection is far longer than thought. It has reached way beyond our reproductive years and zapped most harmful genetic variants before they could get to be common in the population. That leaves relatively uncommon variants, lots and lots of them in each case, as the genetic cause of each common disease.

In the last few years gene hunters in one common disease after another have turned up a few causative variant genes, after vast effort, but the variants generally account for a small percentage of the overall burden of illness. With most common diseases, it turns out, the disease is caused not by ten very common variant genes but by 10,000 relatively rare ones.

Today it’s the turn of schizophrenia researchers to make the same discovery. . . .

Schizophrenia too seems to be not a single disease, but the end point of 10,000 different disruptions to the delicate architecture of the human brain. . . .

So the press release writers could have cast it as a noble defeat, were words like defeat a part of their vocabulary, or frankness their masters’ priority. . . .

So — why asenapine (the chemical name of the drug Hassan proposes to brand as “Saphris“, in the United States), that decidedly old-schoolish Schering-Plough candidate awaiting an FDA decision, later this year (rescheduled from the middle of last year) for treatment of schizophrenia? Because we now know several other large pharma players passed on bringing it to market, before Fred Hassan threw perhaps a half-billion dollars into trying to get it approved — at Schering — for schizophrenia.

Yes, the “defeat points in some measure to the daunting nature of the adversary” — and, in the case of asenapine, perhaps even more to the hubris that leads one CEO to think he could succeed where scores of others have assessed (including Pfizer, quite rightly, it seems) that it wouldn’t be “a major advance“.

Merck Expects to Name the “New Merck” Senior Executives By Late August 2009

Yet another Merck Merger Update was filed this morning with the SEC — and this is the only really “new” information, in the page and a half of text:

. . . .I realize that most employees want to know the outcome of all this work. In other words, what is the new Merck structure and who will be on the new Merck leadership team. We expect to share our new structure and senior leaders (EC+1) by late August. . . .

So, the EMT equivalents will be identified shortly, then their direct reports (EC+1), or one layer below the EC (the equivalent of an EMT at most other pharma companies), will be named by late August.

All of this assumes a vote in favor of the reverse-merger, as presently structured, by both companies’ shareholders, on August 7, 2009.

When to Put a Patient on a Simple Statin? The Role of C-Reactive Protein Questioned — Anew

After Crestor’s Jupiter trial results last year (one of the pivotal events in the decline of Schering-Plough’s Vytorin/Zetia), it was thought, by some, that perhaps c-reactive protein (or CRP) might not only appear as evidence of inflamation associated with heart disease — but elevated levels of CRP might actually be a contributing cause – of heart disease. Not so, apparently, according to a study involving more than 100,000 patients, published in JAMA, just yesterday. [Both Marilyn Mann, and Matt Herper, of Forbes, had speculated that this might be the outcome, last year. They were both right.]

In any event, The New York Times Health Page has done a nice job of summarizing, in plain-English, these latest JAMA-published findings — and the background, on treatments for elevated cholesterol — do go read it all, but here is a snippet:

. . . .C-reactive protein, or CRP, a marker of inflammation in the body, is unquestionably associated with heart disease: the more CRP in a person’s blood, the greater the likelihood of heart disease.

But in a paper to be published Wednesday in The Journal of the American Medical Association, researchers analyzing genetic data from more than 100,000 people conclude that their study “argues against” the notion that the protein causes heart disease. . . .

Different people produce different amounts of CRP, and the amount a person produces is determined by tiny inherited changes in the CRP gene. So in a population, there are people who just happen to produce more CRP throughout their lives and others who just happen to produce less. If CRP causes heart disease, those who make more would have more heart disease. That, however, is not what the study found. . . .

Dr. Rader, at Penn, said he still did CRP tests on selected patients and expected to continue. An elevated CRP level indicates increased risk, even if the protein does not cause the risk. Dr. Rader tests CRP to help decide whether to give a statin to patients with normal cholesterol but with a family history of heart disease. A high CRP, he said, could tip the balance, leading him to prescribe a statin.

Dr. Altshuler noted that part of the power of a Mendelian randomization study was that it could stop a hypothesis from prematurely becoming viewed as fact. . . .

That would be a very good thing — as perhaps hundreds of thousands of patients would not have been rushed onto wildly-expensive regimens of Vytorin/Zetia, in the last four years, when simple, cheap generic statins were apparently doing an adequate job, in the vast bulk of typical cases.

Schering-Plough Posts Positive Phase III Results in Fertility Trial

. . . .However, this was a non-inferiority trial, afterall.