We 'Heart' Biomarkers, Say AstraZeneca and Merck

AstraZeneca and Merck may be battling for dominance in the statin market, but the two heavy-hitters are now putting their heads (and wallets) together to explore the next evolution in heart disease.

The drug giants are teaming up to study biomarkers, the body's biological cues that could play a role in drug discovery and diagnostics.

Although it could be a decade or more before the hope lives up to the hype in this area, the AstraZeneca-Merck initiative highlights one example of the field's potential. Both already big players in the cholesterol market--Merck, which recently lost patent protection on Zocor (simvastatin), still co-promotes Vytorin (simavastatin/ezetimibe) with Schering/Plough, and AstraZeneca sells blockbuster Crestor (rosuvastatin)--the companies are trying to extend the life of their brands by looking beyond LDL. Working with biomarker specialists BG Medicine, health insurer Humana, and Royal Philips Electronics, the two big pharmas are trying to predict--and ultimately stave off--heart attacks.

Each of the companies have contributed about $5 million, for a total of $25 to 30 million. The drug makers will have "full and unrestricted rights" to commercialize any products that the findings yield, but are each working on separate pursuits.

"The real value for them is that it establishes a market for products that wouldn't otherwise be there," said Pieter Muntendam, president of BG.

The research might show, for example, that suppressing a biomarker like inflammation, one of the biggest risk factors for heart attacks, might be more successful in disease prevention than merely controlling high cholesterol. "We can't intervene early [in heart disease]--we can only identify high cholesterol," Muntendam said. "There's been a gradual increase in recognition that this is paradigm is favorable to the pharmaceutical industry [and] drug discovery."

The COX-2 market, while not part of this most recent partnership, might also benefit from biomarker research, Muntendam suggested. It's these subtle changes in cell proteins that differentiate a drug like Vioxx (rofecoxib), which had to be pulled from the market, from Celebrex (celecoxib), the only COX-2 inhibitor still standing. Currently, only large scale studies can show which drug is safest, but it might one day be possible to use animal models to test how these compounds act on specific biomarkers.

"Very often the surprises come in Phase III--or, worse, the adverse effects come about after the drug is on the market," said Muntendam, a proponent of a preclinical testing model that incorporates biomarkers.

Yet there have been some early disappointments. The Framingham Heart Study, for instance, failed to find any clinical benefit for using biomarkers to predict heart attacks--they were only marginally more successful than current screening methods that focus on blood pressure and LDL-levels.

"This is just a huge beast that everyone is looking at," said Greg Stone, media and communications director at Applied Data Research, a drug therapeutics consulting firm. "It's like antibodies 15 years ago--a lot of potential. The real issue relates to validation and identification. The complexity of the body and the genetic variance across the population make [application] difficult."

FDA and the National Institutes of Health have both expressed interest in working with industry to study biomarkers. But most corporate labs aren't set up to handle that sort of research. "It's going to be challenging and slow-going," Stone said.

Muntendam, too, acknowledged that pharma doesn't yet have the infrastructure in place to do large-scale biomarker studies. "The industry is still trying to get its arms around what it is, how to do it," he said. Nevertheless, he added, "There's a tremendous amount of low-hanging fruit, but the research hasn't been done."