November 17, 2010
Merck Drug Improves Cholesterol Without Safety Risk
By Michelle Fay Cortez
An experimental drug from Merck & Co. raised levels of good cholesterol, slashed bad cholesterol and may have helped patients avert heart complications, without the safety risks that prompted Pfizer Inc. to abandon a similar product four years ago.
Patients on the treatment, called anacetrapib, had a 40 percent drop in bad cholesterol and a 138 percent rise in the good cholesterol that ferries fat from the blood, the study found. Sixteen people on the drug died, had heart attacks or strokes, compared with 21 on a placebo. The 1,623 patient trial was funded by Whitehouse Station, New Jersey-based Merck.
The data, reported at the American Heart Association meeting in Chicago, will revive interest in a class of medicines that may reach peak sales of $15 billion a year, said Nikhil Mehta, director of cardiovascular disorders at Decision Resources, a consulting firm. Investors who lowered expectations after the failure of Pfizer’s pill torcetrapib, in a family of medicines known as CETP inhibitors, may now change their view, he said.
“If what we are seeing now is born out in larger studies, this could be the next big thing that could benefit hundreds of millions of people,” said Christopher Cannon, the lead researcher and a cardiologist at Brigham and Women’s Hospital in Boston. “The bad cholesterol goes down to the level you are born with and good cholesterol gets up to twice what you are born with. This is totally unprecedented territory.”
Merck rose 37 cents, or 1.1 percent, to $34.47 at 4 p.m. in New York Stock Exchange composite trading. The shares rose 0.5 percent in the past 12 months.
Roche Holding AG, based in Basel, Switzerland, and Eli Lilly & Co. of Indianapolis have similar drugs in development. Merck said it will begin its final trial of anacetrapib in 30,000 high-risk patients next year
“There’s no reason the sales potential that existed before torcetrapib failed doesn’t apply now,” Decision Resources’ Mehta said in a telephone interview. “No other drugs have taken the place of these medicines. There is still potential for multibillion dollars of sales, going up into the double-digit range. This is an important study for reassuring people and raising the profile of the class again.”
The finding virtually rules out the likelihood that Merck’s pill will have the same toxicity as the failed Pfizer drug, said Steven Nissen, head of cardiology at the Cleveland Clinic in Ohio, who led one of the trials studying the similar Pfizer compound, called torcetrapib.
“There is a very good chance that this drug will make it,” Nissen said in an interview.
Lipitor, which lowers bad cholesterol, or LDL, generated $11.4 billion in sales for New York-based Pfizer last year. The product faces generic competition in the U.S. next year. Torcetrapib, before being abandoned after the company paid $1 billion to develop it, was seen as the next big revenue- generator for Pfizer, the world’s largest drugmaker.
Doctors and drug companies have been searching for years for ways to reduce heart disease with good cholesterol, and the findings are promising, Nissen said.
“This class, if it works, could be as big as the statins,” the class Lipitor belongs to, he said. “If we can reduce event rates another 25 percent above what statins do, that will save a lot of lives.”
Everyone in the study also received potent drugs known as statins to lower bad cholesterol levels. While those medications reduce the risk of heart attack and death by about one-third, heart disease remains the leading killer worldwide, according to the World Health Organization. Statins generated $35 billion in 2009, according to IMS Health Inc., a research company in Norwalk, Connecticut.
The study was also published in the New England Journal of Medicine to coincide with the presentation. There were no signs of increased blood pressure or levels of the hormone aldosterone, which studies suggest may be the cause of torcetrapib’s flaws. In the trial, significantly fewer patients getting anacetrapib needed procedures to clear clogged heart arteries.
While torcetrapib raised good cholesterol levels, it also unintentionally increased blood pressure, electrolytes and the hormone aldosterone. An analysis of the existing data on torcetrapib suggest those so-called off-target effects were the cause of the drug’s toxicity. Merck’s product doesn’t have any of those effects or show signs of other serious adverse events, the researchers said.
“We were able to say very confidently anacetrapib is not associated with increases in blood pressure, as torcetrapib was, electrolytes or aldosterone,” Yale Mitchel, Merck’s vice president of clinical research for atherosclerosis, said in an interview.
Torcetrapib increased the number of deaths in its final study, making that a key issue, said Harlan Krumholz, a cardiologist and professor at Yale University School of Medicine. In Merck study today, four patients taking anacetrapib and one person given a placebo died from cardiovascular causes. While the difference could have stemmed from chance, it is something to watch, he said.
“I’m not saying this will be a dangerous drug, but I’m not sure there will be reduction in deaths,” he said in an interview. “I’m bullish on the idea of testing this, I’m just not bullish about the result. I don’t have enough information.”
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