When Pfizer Inc. abandoned a cholesterol pill four years ago after spending $1 billion to develop it, Richard Clark, Merck & Co.’s chief executive officer, was tempted to give up on a similar drug in testing.
Both companies had spent years pursuing powerful new treatments designed to boost the good cholesterol that ferries fat from the bloodstream even as they reduce bad cholesterol. The goal was to give doctors a new way to combat the world’s biggest killer, cardiovascular disease. Then, in 2006, a study found that Pfizer’s product, torcetrapib, raised blood pressure and caused more heart attacks, not fewer.
New York-based Pfizer stopped developing its product and left Merck, of Whitehouse Station, New Jersey, at a crossroads, Bloomberg Businessweek reports in its Nov. 29 issue. If Merck proceeded with its pill, it risked spending hundreds of millions of dollars more on a failure. If Merck quit, it risked throwing away what might become the world’s most valuable medicine.
“There was a huge debate at every level from the research teams to the top levels of leadership,” said Luciano Rossetti, Merck’s senior vice president of global scientific strategy, in a telephone interview. “It was a high-stakes game.”
The experimental pills are in a new family known as CETP inhibitors. For six months, Merck’s researchers examined and re-examined their version, called anacetrapib, in test tubes and in lab rats. The results came up positive; the drug didn’t raise blood pressure in animals. Clark decided that Merck, a leader in heart research for 50 years, would press ahead.
That gamble paid off. Last week Merck officials told thousands of heart doctors gathered in Chicago for the American Heart Association’s annual meeting that new data showed anacetrapib reduced bad cholesterol by 40 percent. The pill also raised good cholesterol by an unprecedented 138 percent, according to a company-sponsored study of 1,623 patients.
“This is totally unprecedented territory,” said Christopher P. Cannon, a cardiologist at Brigham & Women’s Hospital in Boston and the study’s lead researcher. “If what we are seeing now is borne out in larger studies, this could be the next big thing that could benefit hundreds of millions of people.”
For Merck, after a decade of high-risk research, anacetrapib is one of four cardiovascular treatments in final testing that each have the potential for at least $1 billion in yearly sales by 2016, according to Robert Hazlett, an analyst at BMO Capital Markets in New York. Two of the drugs target cholesterol, and two aim to prevent blood clots.
$35 Billion Market
Pfizer and Merck, the two biggest U.S. drugmakers, have been locked in a 25-year battle to dominate the cholesterol market, one of the highest-stakes pharmaceutical businesses. New drugs in that area cost more than $1 billion each to develop, and worldwide sales last year topped $35 billion, according to IMS Health Inc., a research company in Norwalk, Connecticut.
The standard treatments for high cholesterol, called statins, reduce LDL, the bad cholesterol that clogs arteries and causes heart attacks. In 1987, Merck received regulatory approval to market the first statin, Mevacor. Pfizer followed a decade later with Lipitor, a drug that soon eclipsed Merck’s statins to become the world’s best-selling medicine.
Lipitor has been hard to beat, so pharmaceutical companies in search of new blockbuster drugs have been shifting their research focus to maladies such as cancer and Alzheimer’s disease, where breakthroughs may be easier to come by. In January, Pfizer itself said it would narrow its drug-development pipeline to 500 projects in six illness areas; cardiovascular disease wasn’t one.
That tips the balance in favor of Merck, whose late-stage cardiovascular trials involve about 120,000 patients.
“Our efforts in this field have been uninterrupted,” Merck’s Rossetti said. “We believe that Merck is going to be the leader.”
In the area of preventing blood clots, Merck researchers say their experimental pill called vorapaxar may achieve the ultimate goal of a blood thinner: to lower the risk of heart attack and stroke without causing excessive bleeding.
The company plans to seek U.S. approval of the medicine next year, pending results of a 40,000-patient study. That means the drug might be available around the time Plavix, the leading blood thinner with $10 billion in worldwide sales, is set to go off patent. Plavix is made by New York-based Bristol-Myers Squibb Co. and Paris-based Sanofi-Aventis SA.
Some patients had to be removed from the anacetrapib trial because their bad cholesterol dropped too much; the next study will need to determine if there is a limit where the drug becomes harmful. With vorapaxar, the biggest risk is that along with preventing clots, the blood thinner will cause patients to bleed unnecessarily, BMO’s Hazlett said. As with any drug study, additional risks from either drug may yet arise.
If the drugs aren’t sidelined by side effects, anacetrapib and vorapaxar each have the potential to exceed $5 billion in yearly sales, Hazlett said in a telephone interview. Anacetrapib, if it works in a final study of 30,000 patients, may even accomplish what no other drug in history has been able to do: outsell Lipitor.
“Other organizations have notably pulled back, and to their credit, Merck has continued to focus, taking good, well-calculated bets” Hazlett said. “They are certainly in a position to reap the rewards of that sustained investment.”