Roche Drops After Halting Cholesterol Drug Development
Roche Holding AG (ROG) fell the most in almost six months in Zurich trading after abandoning development of an experimental cholesterol drug as a late-stage trial showed it wasn’t working.
An independent group of experts recommended stopping the study of dalcetrapib “due to a lack of clinically meaningful efficacy,” Basel, Switzerland-based Roche said in a statement today. The company had planned a six-trial development program that could have put more than 35,000 patients on the drug, intended to boost so-called good cholesterol.
The failure may have repercussions beyond Roche, tempting Eli Lilly & Co. (LLY) to write off the good-cholesterol approach, said Tim Anderson, an analyst Sanford C. Bernstein & Co. Lilly and Merck & Co. (MRK) are working on medicines that target good cholesterol. Gbola Amusa, an analyst at UBS AG, had estimated dalcetrapbib could generate $6.8 billion in annual sales by 2020 and given it a one-in-four chance of success.
The heart drug “was potentially one of the largest new assets they had in the late-stage pipeline,” Karl Heinz Koch, an analyst at Helvea SA in Zurich, said by phone. “It does leave a large gap.” He said he maintained his sales forecasts for Roche because he had assumed the medicine wouldn’t work. Koch rates the stock neutral.
Roche fell 3.5 percent to 159.40 Swiss francs at the close in Zurich, the steepest decline since Nov. 21.
Dalcetrapib was one of nine medicines with potential sales of more than 1 billion Swiss francs ($1.1 billion) each that Roche planned to introduce by 2016.
Dalcetrapib’s failure is the latest in a series of trials to raise questions over whether boosting good cholesterol, or HDL, actually helps patients. Pfizer Inc. (PFE) scrapped development of a similar medicine, torcetrapib, in 2006 after fatalities were higher among patients taking it in a study than among those who didn’t. In May 2011, a study found that an Abbott Laboratories (ABT) drug designed to raise good cholesterol didn’t prevent heart attacks.
Still, Roche boosted some investors’ hopes last year when data from a pair of smaller tests showed dalcetrapib didn’t raise blood pressure, setting some safety concerns to rest.
Results from a trial of more than 15,000 patients called dal-Outcomes had been expected to show by next year whether dalcetrapib could help keep patients alive and block heart attacks and strokes in people who had already had acute coronary syndrome. Roche then started recruiting patients in January for what was to have been a 20,000-person test on a broader group of patients, including those at risk for cardiovascular disease who hadn’t had heart attacks yet.
The results may cast doubt on the HDL hypothesis and may mean “all the possible drugs in development that are based on the mechanism will similarly fail,” Erik Gordon, a business professor at the University of Michigan in Ann Arbor, said in an e-mail. “The failure is for lack of efficacy, and that is less fixable than failing due to side effects.”
HDL flushes fat deposits in arteries out of the body via the liver. That’s different from the way statins such as Pfizer’s Lipitor work to decrease levels of bad cholesterol, or LDL, which clogs arteries.
“This is admittedly an important setback for Merck and for the pharma group in general,” Mark Schoenebaum, a New York- based analyst for ISI Group, wrote in a note to clients today. Merck still has a chance of success, though, because its drug anacetrapib works differently than the Roche attempt, Schoenebaum wrote.
Lilly may abandon its compound, which stands at the beginning of a large-scale final-phase trial program, Anderson, an analyst for Sanford C. Bernstein, wrote in a report to investors today. “Lilly may determine that the risk and cost associated with carrying out another mega-trial is simply not worth it given the various uncertainties,” Anderson wrote.
Lilly didn’t respond to e-mailed requests for comment.
“Merck remains confident in our development program for anacetrapib,” Pamela Eisele, a Merck spokeswoman, said in an e- mail.
The Data and Safety Monitoring Board made the recommendation to stop the trial. The board didn’t report safety signals related to the trial, Roche said. The Swiss company licensed dalcetrapib from Japan Tobacco Inc. (2914) in 2004.
The findings don’t close the door on the Merck and Lilly drugs, said Steven Nissen, head of cardiology at the Cleveland Clinic in Ohio. Both raise good cholesterol by more than 100 percent, significantly more than dalcetrapib, and lower bad LDL cholesterol by 35 percent or 40 percent. The Roche drug doesn’t affect bad cholesterol. Nissen is leading research on the Lilly drug.
“What I worry about is the way this gets played out,” Nissen said. “People are starting to say HDL isn’t going to work. We don’t know that yet. It’s too early to bury the HDL hypothesis.”
The studies cost hundreds of millions, if not billions, of dollars. Nissen said he would have told Roche to save its money.
“If Roche had asked my advice, I would have never developed dalcetrapib,” he said. “It was never going to answer the question about the HDL hypothesis.”
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