Shares of Pfizer, a component of the Dow Jones industrial average, plummeted nearly 24 percent before recovering slightly. The stock closed at $25.75, down $3.23 or 11 percent.
"People should go back to aspirin," said Herman Saftlas, a pharmaceutical analyst at Standard & Poor's, which began advising investors yesterday to sell Pfizer stocks. The Celebrex-style drugs are "under scrutiny, and doctors will be very reluctant to prescribe them for anybody with any hint of cardiovascular problem."
Pfizer's surprise announcement helped send the shares of most other drug companies lower yesterday, including AstraZeneca P.L.C. and Eli Lilly & Co. AstraZeneca, which has U.S. headquarters in Wilmington, reported its lung cancer drug Iressa failed a key clinical trial. Shares fell $3.11 to $37.10.
Lilly warned doctors to stop using its attention deficit disorder drug Strattera on patients who showed signs of liver problems or jaundice. Its shares dropped $1.38 to $56.02.
The Cox-2 inhibitors such as Celebrex, Vioxx and Bextra operate on a different process from such pain-relievers as ibuprofen and have become popular in treating arthritis pain and other inflammatory ailments.
Nearly 55 million prescriptions for Cox-2 drugs were written worldwide in 2003, generating U.S. sales of $5.3 billion, according to IMS Health, an industry-monitoring firm with offices in Plymouth Meeting.
Celebrex was a best-seller among them, with 27 million prescriptions and U.S. sales of $2.6 billion in 2003.
Vioxx, which had 20 million users and worldwide sales of $2.5 billion, was withdrawn by Merck voluntarily Sept. 30 after a company-sponsored clinical trial showed increased risk of heart attack and stroke in some patients after 18 months.
The Vioxx withdrawal came after the company had dismissed several studies indicating a problem with its Cox-2 drug. Now, the New Jersey-based Merck, with thousands of employees in the Philadelphia area, faces legal bills projected to run into the billions of dollars.
The Food and Drug Administration also has come under scrutiny over its actions related to Vioxx and other drug approvals. It has scheduled hearings in February on the Cox-2 drugs, which operate by blocking a protein believed to be associated with inflammation.
Scientists have long debated whether the same protein is also responsible for preventing heart problems. The latest study supports the theory that any Cox-2 inhibitor, no matter what its specific chemical design or dosage, may have some effect on the heart.
A nonpartisan watchdog group, Public Citizen, reiterated its call for a ban on Celebrex and another Pfizer painkiller, Bextra, in the same class.
"They should start the process now of taking them off the market," said Sidney Wolfe, a physician at Public Citizen, which publishes a list called Worstpills.com.
However, a prominent critic of the drugs urged a measured response, saying Celebrex may still be useful for certain patients with no heart problems.
"Withdrawing Celebrex would be throwing the baby out with the bathwater," said Garret FitzGerald, a University of Pennsylvania cardiologist and pharmacologist.
"What this does is it ends the controversy as to whether there is a class effect," FitzGerald said. "Now, it's important to put this controversy behind us and deal with reality by trying to avoid the hazard."
Pfizer, which had sales of $45 billion last year, did not address the class question or its other Cox-2 drug, Bextra. In its statement, Pfizer chairman and chief executive officer Hank McKinnell called the trial results "unexpected" and said Pfizer "is taking immediate steps to fully understand the results and rapidly communicate new information to regulators, physicians and patients around the world."
Despite the latest results, Pfizer said it would continue its plans to sponsor another trial with Celebrex, this one on osteoarthritis patients at high risk for cardiovascular disease.
"Another trial with Celebrex at this point would be unethical, period," said Wolfe, from Public Citizen.
Financial analysts appeared mixed on the damage to Pfizer's prospects, with some saying the company might weather the storm if it steps back from Cox-2 drugs until all safety issues are resolved.
"Withdrawal of Celebrex? That would be premature," said Henant K. Shah, an independent health-care analyst based in Warren, N.J. "The smart move now is just to wait."
Prudential Equity Group, in a market commentary, gave the stock a "neutral" rating and noted the increasing likelihood of a problem with all Cox-2 drugs.
Whether proved or not, physicians and patients likely will avoid both of Pfizer's Cox-2 drugs. "Commercially," Prudential said, "Celebrex and Bextra will likely sustain a significant blow."
Contact staff writer Thomas Ginsberg at 215-854-4177 or firstname.lastname@example.org.