UPDATED: New cloud hovers over class of 'good cholesterol' drugs

Fresh doubts have cropped up for raising "good cholesterol" to combat heart attack risk, after a new study showed that patients genetically programmed to have higher levels of HDL cholesterol didn't appear to be more protected from heart disease than those with low levels. The news comes as Merck ($MRK) and Eli Lilly ($LLY) are spending millions of dollars to develop HDL-raising treatments, aiming to deliver on the blockbuster potential of the CETP drug class.

"I'd say the HDL hypothesis is on the ropes right now," said outside observer Dr. James A. de Lemos, a professor at the University of Texas Southwestern Medical Center, as quoted by The New York Times.

The HDL mechanism took a recent blow last week when Swiss drug giant Roche ($RHHBY) announced that it was nixing development of its contender designed to raise good cholesterol to thwart heart disease because of absent efficacy, following previous failures at Pfizer ($PFE) and Abbott ($ABT). Informed of the new genetic study revealed this week in The Lancet, Merck and Lilly representatives told the Times that the companies were both undeterred and continuing with their massive CETP programs. Yet the findings have dampened expectations for the drugs.

"This will have a sobering effect, it would have to," said John LaMattina, a senior partner at PureTech Ventures and former Pfizer R&D chief, as quoted by Bloomberg. "HDL has always been a controversial area. You have a question that you have to be willing to commit over a billion dollars in order to get the answer, and that is a very daunting commitment."

With billions of dollars in development costs and potential revenues on the line, expect scientists inside and outside of biopharma companies to take heed of the findings and dig deeper into the role of HDL in heart disease. As the Times notes, mouse studies showed that HDL carried cholesterol out of the arteries. But scientists will now look into whether HDL is an indicator or driver of reduced heart-attack risk.

Forbes' Matthew Herper reported that the latest HDL paper might not bring much in the way of new doubt about HDL-raising drugs, which were "already on the ropes" because of conclusions from previous studies. And he noted that The Lancet paper shows a slight 4% reduction in heart attack risk among patients with a mutation to the CETP gene, which might give hope to believers in drugs that target the CETP protein.

- read the NYT's article
- and Bloomberg's report
- see Herper's piece

Editor's note: Adds analysis of The Lancet paper from Herper's article. 05/20/12.