【按】我以前提过一个观点：提高英语阅读和写作能力的最佳读物是《华尔街日报》。可惜的是这份报纸在网上不是免费的，在美国也不是所有公司的电脑都能登录阅读。今天《华尔街日报》刊登了一条与制药业有关的重大新闻，美国辉瑞制药的一个重要新产品不幸夭折于第三期临床试验，损失无比惨重！该报记者继今年夏天报道庞加莱猜想之后又一次使用了"throw a (monkey) wrench into"这一如今已经非常有名的英语成语，无非这次将“猴子扳手”简化为“扳手”。在此仿照古龙小说的标题转贴一下该报道的开头部分。

Demise of a Blockbuster Drug Complicates Pfizer's Revamp

Failure Is a Blow for Promising Heart-Disease Treatment After Deaths in Trials

Special Pancakes Put on Hold

By SCOTT HENSLEY and RON WINSLOW
December 4, 2006; Page A1

The demise of a potential blockbuster drug designed to replace the powerhouse Lipitor throws a wrench into the plans of Pfizer Inc. Chief Executive Jeffrey Kindler to remake the world's biggest drug company.

Late Saturday, Pfizer said it was stopping development of torcetrapib, a drug that helps boost the production of so-called good cholesterol, a technique thought to offer promise for the treatment of heart disease. During a clinical test involving 15,000 patients, more people than expected died while taking the experimental medicine.

The announcement raises new questions about one of the pharmaceutical industry's most anticipated new ideas. Several companies have made investments in this area in the hunt for badly needed sales and profit growth.

Just two days earlier, in an upbeat presentation to analysts, Pfizer research chief John LaMattina reiterated the company's backing for the compound. "We believe this is the most important new development in cardiovascular medicine in years," he said.

But a phone call to Dr. LaMattina from a Pfizer colleague early on Saturday delivered stunning news: Some 82 patients taking torcetrapib and Lipitor had died, compared with 51 taking Lipitor alone. Those findings had come from a monthly review completed late Friday night by the independent safety board monitoring the trial.

Besides the deaths, patients taking torcetrapib also showed an increase in angina, congestive heart failure and procedures to clear clogged arteries. Dr. LaMattina called Mr. Kindler, prompting emergency meetings at Pfizer's offices. "There wasn't much of a discussion," Mr. Kindler recalls. "It was clear we had to stop the trial."

Pfizer, like many of its rivals, is being buffeted by an anemic near-term pipeline of promising new drugs, patent expirations on long-standing blockbusters and cost-cutting demands from insurers, employers and the government. Doctors and patients are under pressure more than ever before to use the growing list of effective generic medicines instead of the industry's more lucrative brand names.

In the three-year period ending in 2007, New York-based Pfizer will see blockbuster drugs with $14 billion in peak annual sales lose their patent protection. In a recent report, Richard Evans, an analyst at Sanford C. Bernstein, estimated that Pfizer's sales will slip from $47.1 billion this year to $41.7 billion in 2008. The erosion will worsen without torcetrapib, which some optimists had projected to arrive in 2009.

For its part, Pfizer affirmed Saturday that revenues for the next two years would be "comparable" to 2006 and that revenue growth would resume in 2009, despite the termination of research and development of torcetrapib.

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Pfizer rose to the top of the pharmaceutical industry largely on the strength of Lipitor, which along with its rivals became one of the world's best-selling class of medicines in the past two decades. Its ability to lower bad, artery-clogging cholesterol, known as LDL, has led to substantial reductions in heart attacks and death, transforming cardiology in the process.

Despite that success, coronary artery disease remains the world's leading killer, and as many as half of heart-attack victims have LDL levels that were considered normal. As it turned out, many of those patients also had low levels of HDL, or good cholesterol, which helps clear arteries of the bad kind.

More than 50 million Americans, about 25% of the adult population, have low HDL, according to the American Heart Association. In patients tracked by the long-standing Framingham Heart Study, a single milligram increase in HDL is associated with a 2% to 3% reduction in a 10-year risk of a heart attack. All of that is a big reason why pharmaceutical companies have been looking for a drug that raises levels of HDL.

Pfizer's efforts to develop an HDL-raising drug began in 1990 after a paper was published in the New England Journal of Medicine showing no evidence of early heart disease among a dozen Japanese families with high HDL. The decision to develop torcetrapib was one result, and in 1999 it was first given to humans.

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Torcetrapib was the first in a new class of compounds known as CETP inhibitors, which target the cholesterol ester transfer protein. That protein regulates how HDL helps flush away bad cholesterol from the body, theoretically reducing the buildup of heart attack-causing plaque in blood vessels. The connection between raising HDL and preventing heart attacks, however, has been hard to prove conclusively.

Torcetrapib's failure is the latest in a string of disappointments for blockbuster heart drugs late in the development cycle. Among them: AstraZeneca's PLC's blood thinner Exanta and Bristol-Myers Squibb Co.'s blood pressure drug Vanlev.

Despite billions in research and development over the past two decades, one of the last major breakthroughs in cardiovascular disease was the introduction of the first cholesterol-lowering drug, called a statin, in 1987, says Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

"We haven't really had a game-altering strategy for beating this disease since then," Dr. Nissen says. "Torcetrapib was the one that was on everybody's mind. It is a great disappointment...that we're not going to have this drug." Pfizer has two backup candidates in development, but they are still in the first stages of human testing.

Pfizer's bad weekend started Saturday at 7 a.m. when the phone rang at the home of Pfizer research chief Dr. LaMattina in the Connecticut seaside town of Stonington. Dr. LaMattina says he was taking a shower and feared an early call might mean something was wrong with one of his kids. Wrapped in a towel and dripping wet, he walked from the bathroom to his home office to pick up the phone.

Steven Ryder, a Pfizer executive in charge of development for torcetrapib, delivered the bad news. The magnitude of the excess deaths among patients had triggered a recommendation to halt clinical testing.

Dr. LaMattina couldn't believe it. "My first reaction was 'huh?'" he said. "I was stunned and had to sit down." He said no one had expected the drug to be canceled.

A few minutes later, Dr. LaMattina called Mr. Kindler at his house across the state in Westport, both men recall. Mr. Kindler was preparing to celebrate his daughter's 18th birthday. By family tradition, he and his wife were going to make pancakes for his daughter in the shape of her initials. Instead, he says he woke her up and told her goodbye.

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