ENHANCE Interrogation Technique

So what was our colleague Ramsey Baghdadi's "little birdie" talking about when s/he said to expect "something big" to get released this week?

Maybe it was yesterday's encore public throttling of Avandia in the Journal of the American Medical Association. That study concluded that older (age 66+) patients on Avandia had "an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments."

But we're not so sure--the sequel is rarely as good as the original, and why would anyone be whispering to a journalist about a study that was probably available on an embargoed basis anyway.

Perhaps instead our avian friend was referring to the latest chapter in the ENHANCE saga? Yesterday Schering-Plough's Fred Hassan and Merck's Dick Clark got some mail from the House Committee on Energy and Commerce, and it wasn't a Christmas card.

The letter, from committee chairman John Dingell (right) and subcommittee on oversight and investigations chair Bart Stupak, both Michigan Democrats, questions the companies' delay in releasing data from the ENHANCE study, which concluded in April 2006. ENHANCE was designed to compare the efficacy of Vytorin (ezetimibe [Zetia] plus simvastatin) and simvastatin alone.

Merck and Schering-Plough have five billion reasons to hope Vytorin does a better job of preventing plaque buildup in the arteries than now-generic simvastatin, and a combination of the significant and multiple delays in releasing data from the 720-patient trial, a delay in registering the trial with clinicaltrials.gov, and the apparent manipulation of the trial's primary endpoint drew the Congressional attention.

As the WSJ's Health Blog reports, both companies are still reviewing the letter and have yet to repond. For now, they say the data will be released at next March's American College of Cardiology meeting. Meanwhile, Dingell and Stupak contend the pharmas have some explaining to do.

But who knows, maybe that little birdie has something else up its sleeve.

The More The Money-er

The more Epogen, that is.

Just when you thought it wouldn't get any worse for Amgen, a new study published in the Journal of the American Medical Association suggests that for-profit dialysis chains are routinely administering higher doses of Epogen than necessary, thanks to the incentivizing nature of Medicare reimbursement.

Larger doses mean more cash for the dialysis centers, but may boost red blood cells beyond what FDA considers safe. New guidelines suggest going beyond the recommended maximum 12g/dL may cause "an increased number of deaths and of non-fatal heart attacks, strokes, heart failure, and blood clots." All four of the largest for-profit chains administered siginificantly more epoetin than the largest non-profit chains, according to the study.

The more epoetin used in dialysis-related anemia (where the market is all Amgen's), the more profit. And epoetin use is certainly on the rise. According to the study:

"... between 1991 and 2005, the mean dose of epoetin increased about 4-fold in dialysis patients. Today, epoetin therapy is the largest single Medicare drug expenditure totaling $1.8 billion in 2004 (an increase of 17% from 2003) and epoetin comprised 11% of all Medicare ESRD costs."

As we noted last week upon the escape of Amgen CFO Richard Nanula, and as the usual suspects in the pharma blogosphere point out, things are far from rosy at Amgen these days, where the stock is at a 2-year low. FDA warnings, safety concerns across the board, lawsuits, even potential biogeneric competition: Amgen's EPO franchise is under siege. We'll take a look at where the Big Biotech will turn next in the May IN VIVO.