A second experimental cholesterol medicine in a once-promising class of drugs meant to replace blockbusters such as Lipitor has failed in testing, casting doubt on whether any of the drugs will ever make it to pharmacies.

Swiss drugmaker Roche Holding AG said Monday it has halted testing of its dalcetrapib, which the company had hoped would become a blockbuster, with eventual annual sales of more than $1 billion. The drug was in expensive late-stage patient testing as a treatment to raise HDL, or so-called good cholesterol, in heart disease patients.

Basel-based Roche said it decided to pull the plug on the recommendation of its independent data and safety monitoring board after an interim analysis, in a study called dal-OUTCOMES, found no "clinically meaningful" benefit.

The best-known drug in that class, called CETP inhibitors, was Pfizer Inc.'s torcetrapib. It was scrapped five years ago due to safety problems. Merck & Co. and Indianapolis-based Eli Lilly and Co. both are developing drugs in the class. Merck's anacetrapib is in a huge late-stage study, and Lilly's evacetrapib will soon begin late-stage testing.

The CETP class once was seen as successors to the heavily advertised cholesterol-lowering statins taken by tens of millions of people to prevent plaque from building up in arteries and later triggering heart attacks and strokes. Those drugs, which collectively have racked up hundreds of billions of dollars in sales but mostly have generic competition now, include Lipitor and Crestor, plus the older drugs Zocor, Mevacor and Pravachol.

Testing of CETP inhibitors has been among the most expensive drug development programs even though not everyone was convinced they were a good bet, Bernstein Research analyst Dr. Tim Anderson noted Monday.

"Experts in the field of cholesterol management have remained uncertain about the general approach of raising HDL-cholesterol through CETP inhibition. Investors have also remained cautious," Anderson wrote to investors Monday.

Roche, the sixth-biggest drugmaker globally, said that two other late-stage studies of its dalcetrapib have been completed and three other studies were ongoing. Still, the company decided to terminate the drug's entire testing program.

"While we have always stated that dalcetrapib is a high-risk project, we are disappointed by the fact that this drug didn't provide benefit to the patients in our study," Dr. Hal Barron, Roche's chief medical officer and head of global product development, said in a statement, adding that Roche has a robust pipeline and is committed to developing new heart medicines.

Merck spokeswoman Pam Eisley said the company "remains confident in our development program for anacetrapib." A huge study called REVEAL that started last spring is enrolling 30,000 patients to see whether anacetrapib prevents heart attacks and strokes when added to a statin. Results aren't expected for several years. Another late-stage anacetrapib study already completed found it boosted good cholesterol by well over 100 percent and lowered bad cholesterol about 40 percent.

Merck pioneered the statin category with the first drug, Mevacor, and then followed up with Zocor, which was its top seller until generic competition hit in June 2006.

Meanwhile, Lilly said the company is committed to its evacetrapib and plans to start a late-stage study in the second half of this year. Spokeswoman Christina Gaines noted earlier testing showed evacetrapib raises good cholesterol up to 129 percent and reduces bad cholesterol by up to 36 percent, depending on dose.

Statins for years were among the most heavily prescribed drugs in developing countries, where heart disease is a top killer. Pfizer's Lipitor reigned as the top-selling drug in history for about eight years, with peak sales of $13 billion in 2006, but it got limited U.S. generic competition in December. By then, inexpensive generic versions of Zocor and the other older statins already had been nibbling at revenue for Lipitor, which will plunge when multiple generic versions hit drugstores on May 31.

Pfizer, the world's biggest drugmaker, had made it a priority to find a successor before the patent expired on Lipitor, which brought in about a quarter of its revenue from 2004 through 2009. But its heavily touted torcetrapib flamed out early in 2007, after roughly $800 million in testing, because it raised risk of heart attacks and strokes. That failure, along with a general decline in productivity from Pfizer's sprawling research labs, was widely seen as among the reasons the company spent $68 billion to buy fellow drugmaker Wyeth in 2009 and Pfizer's board forced out CEO Jeffrey Kindler in December 2010.

The pharmaceutical industry is challenged by "lagging R&D productivity and various ongoing/upcoming patent expirations on major drugs across the majority of drug companies," Anderson wrote.

He added that if all the CETP inhibitors and two closely watched drugs being developed to slow progression of Alzheimer's disease also fail, "investor patients could again be tested."