Americans' high incidence of cardiovascular disease and obesity has made the development of cholesterol medications one of the most lucrative segments of the drug industry.
So although the failure of a once-promising experimental drug from Pfizer Inc. is a setback, it is unlikely to damp rival development efforts. In the long run, medical experts and market analysts said Monday, the giant firm's competitors as well as cardiovascular patients may benefit as the industry absorbs the lessons of Pfizer's experience.
The focus of Pfizer's testing, torcetrapib, was the most prominent member of a new class of prescription drugs that increase so-called good cholesterol. Good cholesterol is believed to help clear the arteries of fat deposits, or plaque, that build up in people with high levels of "bad" cholesterol.
Currently, the most popular drug therapy for those at high risk for cardiovascular disease is statins, drugs that lower the patient's level of bad cholesterol. Medical scientists believe that a successful combination of the two types of drugs could further cut the risk of death from heart disease, the nation's biggest killer.
But Pfizer's tests, which included torcetrapib alone and in combination with statins, caused an alarming number of deaths and complications among trial patients. The company halted testing Saturday.
Pharmaceutical companies have long been criticized for marginally improving existing drugs to create or protect patented brands and thus charge more for their products. But in torcetrapib's case, doctors agree, the potential benefits were significant.
Although torcetrapib's failure casts doubt on the combination approach, other drug companies, notably Roche Holding and Merck & Co., are likely to continue their own research into similar methods.
"The opportunity is still there. It is a huge market," said Chris Wright, a managing principal of ZS Associates, a pharmaceutical consulting company. "It is bad news for Pfizer because they were so far ahead [in their research]. But in some ways, the race is back on for others."
Treatments that lower the risk of heart disease account for the biggest share of prescription drug sales worldwide, $32.4 billion last year and growing nearly 7% a year, according to industry researcher IMS Health. Pfizer's Lipitor, a statin, is the world's top prescription drug, with nearly $13 billion in sales last year.
Lowering bad cholesterol levels in the blood with statins decreases a patient's risk of heart attack or stroke by about a third, doctors say. Statins, which emerged in the 1990s, are credited with reducing deaths related to cardiovascular disease, but more than 910,000 Americans died from such conditions in 2003, the most recent data show. That's the most from any disease, according to the American Heart Assn.
Several companies launched their own statins, but the drugs are not likely to be improved, partly because they have reached their chemical potential, experts say. Moreover, many, including Lipitor, are expected to lose their patents before the end of the decade. Pharmaceutical companies have little incentive to invest in products that will face growing competition from cheaper generic versions.
Another widely used statin, Merck's Zocor, lost its patent protection this year, and sales have fallen off.
Thus, drugs that can raise good cholesterol are "the new frontier," said Daniel Fisher, a cardiologist at New York University Medical Center. "And it may still be, if you can get it right."
With torcetrapib's failure, a Food and Drug Administration official said Monday that the agency would more closely scrutinize other drugs seeking to raise good cholesterol.
A Roche spokesman said Monday that patients testing the Swiss drug maker's formula had not suffered high blood pressure, one of the complications that undermined Pfizer's trial.
But Roche's research is still in an early phase. Pfizer's research did not detect serious problems until much later in its testing. The company had hoped to introduce its drug to the market as soon as 2009.
The bad news pushed Pfizer shares down $2.96, or 10.6%, to $24.90 on Monday.
Steven Nissen, president of the American College of Cardiology and the principal medical investigator in Pfizer's trial, said it would be months before researchers knew what caused trial patients taking the new drug in combination with statins to die in higher numbers: 82, compared with 51 of those taking only statins.
It is possible that the entire approach of raising good cholesterol while cutting bad cholesterol doesn't work, Nissen said. Or there may be a problem unique to torcetrapib.
What the inquiry finds could help Roche and others, said Robert Goldberg, vice president of the Center for Medicine in the Public Interest, a policy research group.
"They will be mining [Pfizer's] data to see what they can glean and adapt their clinical trials accordingly," he said. "Science is not about home runs. There are a lot of singles and doubles. This was a long out, but every time you go up against a pitcher, you learn something."
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Cholesterol drugs are the world's biggest-selling prescription medications . . .
Leading classes of drugs, ranked by global 2005 sales (In billions)
Cholesterol and triglyceride reducers: $32.4
Cytostatics (for treatment of tumors): $28.5
Antidepressants and mood stabilizers: $19.8
Angiotensin-II inhibitors (high blood pressure): $14.2
Erythropoietin products (anemia): $12.3
Calcium antagonists plain (strokes): $11.9
Oral anti-diabetics: $10.7
. . . with Pfizer's cholesterol treatment Lipitor the
world's bestselling prescription drug
Leading drugs, ranked by global 2005 sales (In billions)
*--* Drug Primary maker Purpose Sales Lipitor Pfizer Cholesterol $12.9 Plavix Bristol-Myers Squibb, Blood thinner $5.9 Sanofi-Aventis Nexium AstraZeneca Heartburn/ulcers $5.7 Seretide/Advair GlaxoSmithKline Allergies $5.6 Zocor* Merck Cholesterol $5.3 Norvasc Pfizer High blood pressure $5.0 Zyprexa Eli Lilly Schizophrenia $4.7 Risperdal Janssen Schizophrenia $4.0 Ogastro/Prevacid TAP Pharmaceutical Heartburn/ulcers $4.0 Effexor Wyeth Depression $3.8
*Zocor lost its patent this year and sales have dropped.
Sources: IMS Health, Times research