Friday, February 18, 2005

FDA PANEL HEARS EXPERT OPINIONS ON COX-2 INHIBITORS

The Food and Drug Administration advisory panel's three-day meeting to review the safety of COX-2 inhibitors is scheduled to conclude Friday.

On Wednesday, the panel heard from drug makers and independent researchers regarding the possible cause of increased cardiovascular risks associated with Merck & Co. Inc.'s painkiller, Vioxx (rofecoxib), which was withdrawn from the market last fall. Experts offered varying scientific explanations for the problem and did not agree on which patients might still need COX-2 inhibitors, The Wall Street Journal reported.

Dr. Garret FitzGerald, a professor at the University of Pennsylvania, said the entire class of drugs is linked to an increased risk of myocardial infarction and stroke, but they may also protect the stomach. He concluded that merely taking smaller doses of the drugs would not solve the problem and that regulators should "leave it to the patient-doctor relationship to define individual behavior."

In its presentation, Merck agreed that the problems may be related to the entire drug class but that it was not clear whether the risks are associated only with COX-2 inhibitors or with older painkillers as well.

Pfizer Inc. presented a new analysis of trials showing that its arthritis drug Celebrex (celecoxib) is not linked with higher cardiovascular risks. The company said it does not agree with the theory that all COX-2 inhibitors carry these risks.

On Thursday, Dr. David Graham, associate director for science and medicine at the FDA's Office of Drug Safety, presented new data on the drug class, concluding that each drug should be separately evaluated. Graham added, however, that he believes the risks involve the entire class.

A Reuters article quoted Graham as saying, "The bottom line conclusion I came to is there really doesn't appear to be a need for COX-2 [inhibitors] . . . I believe there is a [heart] effect and it's dose related."

Graham originally said he would not present at this meeting because FDA officials did not want him citing unpublished findings he derived after examining data on more than 15,000 heart patients in Medi-Cal, California's Medicaid program. According to The Journal, Graham thanked Dr. Lester Crawford, new director of the FDA, for making it possible for him to present.

Graham said data from the study linked higher doses of Celebrex to a "probable increased risk" of MIs but associated "no apparent effect" with doses of 200 mg or less, according to Reuters. He went on to say that Pfizer's Bextra (valdecoxib), when taken at approved doses of up to 20 mg, does not appear to have this risk, but he also cautioned that the findings were based on a small amount of data.

Graham's review found Vioxx to have a "definite" increased risk of MI in doses higher than 25 mg. Although Merck's study suggested the risk did not occur until after 18 months of continuous use, Graham said it is "apparent during days one to 30 of use."

Graham also presented preliminary data on Abbott Laboratories' Mobic (meloxicam), which, according to Reuters, has become a popular replacement for Vioxx. Graham's data suggest Mobic may also have an "increased risk" for MIs.

Boehringer Ingelheim Pharmaceuticals Inc., Mobic's manufacturer, said it has seen nothing in its post-marketing data that indicates "excessive cardiovascular risk."

A Dow Jones report said dozens of physicians and members of the public urged the FDA panel to keep COX-2 inhibitors on the market, saying these drugs are the only ones that alleviate pain without causing stomach problems. A few patients even said they wished Vioxx was still on the market and that they would risk a potential MI to stop their pain.

The FDA panel will continue to hear presentations through Friday and is scheduled to vote on whether it believes the drugs should be taken off the market or just have stronger warning labels.

Following a similar meeting to review safety concerns regarding COX-2 inhibitors, the European Medicines Agency issued safety restrictions Thursday for the entire drug class, including a contraindication in patients with ischemic heart disease or stroke.

Wednesday, February 16, 2005

NEJM PROVIDES EARLY RELEASE OF DATA FROM THREE STUDIES OF COX-2 INHIBITORS

The New England Journal of Medicine (NEJM) posted details on its Web site Tuesday from three studies showing that COX-2 inhibitors increase the risk of serious cardiac events.

The NEJM said it released the information ahead of its regularly scheduled March 17 issue because of "potential public health implications."

Dr. Robert Bresalier, author of the NEJM study on Merck & Co. Inc.'s Vioxx (rofecoxib), told Reuters he believes the entire drug class is at risk of being pulled by the Food and Drug Administration.

"I think the loss of some of these pharmaceutical brands will create a void," Bresalier said, adding that data to be published later this year show Vioxx works at least as well as aspirin in preventing colon cancer.

In a Reuters report, however, NEJM editor Dr. Jeffrey Drazen said that with the available alternatives to COX-2 inhibitors, "it is reasonable to ask whether the use of the drugs can now be justified."

Bresalier's study included 2,586 patients with a history of colorectal adenomas who were randomized to receive either 25 mg/day of Vioxx or placebo to assess the risk of recurrent neoplastic polyps. Bresalier and the other authors found that after 18 months, Vioxx-treated patients had almost twice the risk of having a thrombotic event.

In a second study, authors reviewed all potentially serious cardiovascular events among 2,035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing 200 mg and 400 mg doses twice daily of Pfizer Inc.'s Celebrex (celecoxib) to placebo for the prevention of colorectal adenomas.

The authors found that patients receiving the 200 mg dose of Celebrex had more than twice the risk of having a serious cardiovascular event compared with the placebo group, while the 400 mg group had more than three times the risk of those receiving placebo.

A third study looked at the effects of Pfizer's Bextra (valdecoxib) and its intravenous prodrug, parecoxib sodium, in 1,671 heart surgery patients.

The authors found that 7.4 percent of patients who received a combination of Bextra and parecoxib or a combination of Bextra and placebo had at least one confirmed adverse event versus 4 percent of those who received placebo alone.

Tuesday, February 01, 2005

KAISER PERMANENTE PLACES MORATORIUM ON BEXTRA PRESCRIPTIONS, ACCORDING TO REPORT

Kaiser Permanente has stopped dispensing Pfizer Inc.'s Bextra (valdecoxib) pending further safety data.

According to the Associated Press, a Kaiser memo issued late Friday cited "compelling" evidence regarding elevated cardiovascular risk associated with Bextra and Merck & Co. Inc.'s withdrawn COX-2 inhibitor, Vioxx (rofecoxib).

A Kaiser spokesperson said this is the first time the company's physicians have decided to stop prescribing a drug approved by the Food and Drug Administration. The "moratorium" on new prescriptions for Bextra begins Feb. 1; refills will no longer be dispensed as of March 1. Physicians will be provided with suggestions for alternative therapies to prescribe.

"This is not a drug that saves lives," Dr. Sharon Levine, who supervises medication usage for Kaiser's Northern California division, told the AP. "It's a drug that provides a modest degree of pain relief--no better than Motrin--and the size of the risk, given the benefit provided, did not seem warranted."

The Kaiser memo indicated that the moratorium on Bextra will last at least six months, or "until the FDA and/or Pfizer can provide substantiated evidence to support [the drug's] cardiovascular safety."

Kaiser Permanente is the nation's largest not-for-profit managed-care provider.

Thursday, January 20, 2005

PFIZER REPORTS STRONG Q4, FY 2004 FINANCIAL PERFORMANCE, BUT FALLS BELOW EXPECTATIONS

Pfizer Inc. reported an increase in revenue and net income during the fourth quarter and full year of 2004, as sales of cholesterol-lowering drug Lipitor (atorvastatin calcium) helped to offset generic competition. However, earnings per diluted share for the fourth quarter failed to meet analysts' expectations.

Including more than $1.5 billion in charges, net income during the fourth quarter of 2004 was $2.83 billion, or $0.38 per diluted share. Excluding the charges, adjusted income grew 16 percent from the fourth quarter of 2003 to $4.39 billion, or $0.58 per share. Analysts polled by Thomson First Call had expected $0.59 earnings per share before one-time charges, according to The Wall Street Journal.

For the fourth-quarter 2004, Pfizer posted a 7 percent increase in revenue to $14.92 billion from $13.98 billion one year ago. This included a 23 percent rise in Lipitor sales to $3.26 billion. Sales for COX-2 inhibitors Celebrex (celecoxib) and Bextra (valdecoxib) rose 24 percent to $1.01 billion and 57 percent to $417 million, respectively.

For the full-year 2004, net income was $11.36 billion, or $1.49 per share, including charges. Full-year adjusted income excluding charges increased 31 percent from 2003 to $16.14 billion, representing a 25 percent rise in earnings per share to $2.12. Full-year revenue rose 17 percent from $44.74 billion in 2003 to $52.52 billion in 2004.

The company noted that its strong 2004 performance extended across all therapeutic areas, but especially throughout its cardiovascular/metabolic portfolio.

"Among many solid product performances, Lipitor continued to achieve strong double-digit revenue growth and became the world's first 10-billion-dollar pharmaceutical brand," said Dr. Hank McKinnell, chief executive officer of Pfizer.

"While Pfizer's revenue and income growth will likely be tempered in the near term due to patent expirations and other factors, the company will continue to make the investments necessary to sustain strong longer-term growth, the prospects for which remain excellent," David Shedlarz, executive vice president and chief financial officer, concluded.

Shares of Pfizer closed at $24.88, down $0.42, or 1.7 percent, in moderate trading on the New York Stock Exchange

Friday, January 14, 2005

FDA ASKS PFIZER TO DISCONTINUE USE OF MISLEADING CELEBREX, BEXTRA DTC TELEVISION, PRINT ADS

The Food and Drug Administration sent a letter to Pfizer Inc. stating the direct-to-consumer television and print advertisements for its arthritis-related pain management drugs Celebrex (celecoxib) and Bextra (valdecoxib) are misleading.

The agency's Division of Drug Marketing, Advertising and Communications reviewed a total of five promotional pieces for the COX-2 inhibitors and informed Pfizer that the ads "variously: omit material facts, including the indication and risk information; fail to make adequate provision for the dissemination of the FDA-approved product labeling; and make misleading safety, unsubstantiated superiority and unsubstantiated effectiveness claims."

The letter stated that such omission or minimization of the risks associated with Celebrex and/or Bextra in the promotional pieces is a public health concern because the drugs are contraindicated for several patient populations.

The FDA requested that Pfizer immediately terminate the use of the identified promotional materials and submit a written response to the letter by Jan. 26 describing the company's intentions to comply with the request. Specifically, the FDA asked for a listing from Pfizer of all promotional items for Celebrex and Bextra that "contain claims or presentations the same as or similar to those described" in the letter, along with a plan for discontinuing use of the ads.

Pfizer spokesperson Mariann Caprino said the Celebrex ads cited in the letter "were no longer running," according to a Reuters report.

Friday, December 10, 2004

PFIZER MUST ADD NEW WARNING TO BEXTRA, FDA SAYS

Pfizer Inc. will be required to add a new warning label to its COX-2 inhibitor Bextra (valdecoxib), the Food and Drug Administration announced yesterday.

The new label will warn of possible heart and blood clotting problems, especially in patients who have recently had coronary artery bypass graft surgery (CABG), the FDA said.

According to the FDA, the new label comes in light of a study involving more than 1,500 patients who recently had cardiac surgery. The study found that those treated with Bextra for pain were more likely than those who did not receive drugs to have blood clots and heart problems.

The label will also strengthen the warning about possible serious skin conditions, including Steven-Johnson Syndrome and toxic epidermal necrolysis, both of which can cause death. The FDA said it will strengthen this warning because it continues to receive reports of these serious skin reactions.

Despite the new and modified warnings, the FDA still recommends the appropriate use of Bextra for arthritis and menstrual pain.

"FDA believes that, based on what we know now, the overall benefit of Bextra outweighs the risk when used in properly selected patients as directed in the approved labeling," the FDA said on its Web site.

Monday, December 6, 2004

MOST MEDICAID ENROLLEES SWITCHED FROM VIOXX TO CELEBREX, BEXTRA IN OCTOBER, TRACKING SERVICE SHOWS

After Merck & Co. Inc.'s Vioxx (rofecoxib) was taken off the market in September, most patients who had been taking the drug switched to Pfizer Inc.'s COX-2 inhibitors Celebrex (celecoxib) and Bextra (valdecoxib), according to Verispan's Vector One: State Medicaid Service.

The Vector One tracking service monitors patient and prescription metrics for the Medicaid market, capturing key patient metrics like new, continuing and switch/add patients.

Of the estimated 22,465 Medicaid enrollees who switched from Vioxx in October, 42 percent were prescribed the pharmaceutical brand Celebrex and 24 percent were prescribed Bextra.

Another 10 percent of the switches were made to the nonsteroidal anti-inflammatory drug (NSAID) Mobic (meloxicam), which is manufactured by Boehringer Ingelheim Pharma KG and co-marketed by Boehringer and Abbott Laboratories. Most of the remaining 22 percent of patients were switched to generic NSAIDs.

The service projected that the number of Medicaid enrollees taking Celebrex increased 9 percent to 77,497 between September and October, while Bextra use rose nearly 21 percent to 31,700 patients.

State results differed slightly from these national figures. In October, 4,583 patients switched from Vioxx under California's Medi-Cal program. Nearly 51 percent changed to Celebrex and 19 percent moved to Bextra. In New York's Medicaid program, 39 percent and 27 percent of the 3,531 Vioxx switches were to Celebrex and Bextra, respectively.

Verispan, formed as a joint venture between Quintiles Transnational Corp. and McKesson Corp., provides information products and services.

Wednesday, November 24, 2004

SENATOR TO INTRODUCE LEGISLATION MAKING FDA OFFICE OF DRUG SAFETY MORE INDEPENDENT

The Food and Drug Administration's Office of Drug Safety is too closely linked with the agency's Office of New Drugs, according to one U.S. senator, who said he intends to submit legislation that would make them independent of each other, Reuters reported.

Sen. Charles Grassley, R-Iowa, who chaired last week's Senate Finance Committee hearing relating to the withdrawal of Merck & Co. Inc.'s Vioxx (rofecoxib), said the safety office is too much under the control of those who review New Drug Applications.

During last week's hearing, the associate director for science in the Office of Drug Safety, Dr. David Graham, expressed a similar point of view, according to Reuters. As reported, he testified that the FDA pressured him to alter findings of a study regarding Vioxx and said the agency is incapable of protecting the country against a similar safety issue. Graham also listed five currently marketed drugs that he believes may present safety problems, including Abbott Laboratories' obesity drug Meridia (sibutramine), AstraZeneca Plc's cholesterol drug Crestor (rosuvastatin), GlaxoSmithKline Plc's asthma drug Serevent (salmeterol), Pfizer Inc.'s COX-2 inhibitor Bextra (valdecoxib) and F. Hoffmann-La Roche Ltd.'s acne pharmaceutical brand Accutane (isotretinoin).

The Finance Committee oversees Medicare and Medicaid, programs that spend billions of dollars on prescription drugs. However, it has no jurisdiction over the FDA.

Friday, November 19, 2004

GRAHAM SAYS FDA INCAPABLE OF PROTECTING U.S. FROM SAFETY ISSUES; LISTS FIVE DRUGS WITH SAFETY CONCERNS

At a hearing before the U.S. Senate Finance Committee, Dr. David Graham testified that the Food and Drug Administration pressured him to alter findings of a study regarding Merck & Co. Inc.'s recently withdrawn Vioxx (rofecoxib) and is incapable of protecting the country against a similar safety issue. Graham also listed five currently marketed drugs that he believes may present safety problems.

Graham, a medical officer at the federal agency, presented a study in August that showed Vioxx poses a greater cardiovascular risk than Pfizer Inc.'s similar arthritis drug Celebrex (celecoxib). Prior to the study being presented in Bordeaux, France, at a meeting of the International Society for Pharmacoepidemiology, however, Graham was pressured by senior FDA management to alter his conclusions, the medical officer testified.

The FDA issued a statement that contradicts Graham's account, saying, "Some FDA scientists questioned some of the conclusions in the abstract and, as a result, [Graham] voluntarily chose to revise his conclusions, and he did so, in his own words, 'without compromising my deeply held convictions.'"

The FDA release further stated that Graham was asked to submit a draft report of his findings upon his return from France, but he failed to do so until after the COX-2 inhibitor had already been withdrawn from the market.

Graham also testified before the Committee that the FDA is "incapable of protecting America against another Vioxx" because of bureaucratic torpor and calcified policies, TheStreet.com reported. He further stated that the FDA has a bureaucratic culture in which "post-marketing safety is an afterthought."

He specifically called into question the safety of five currently marketed name brands: Abbott Laboratories obesity drug Meridia (sibutramine), AstraZeneca Plc's cholesterol drug Crestor (rosuvastatin), GlaxoSmithKline Plc's asthma drug Serevent (salmeterol), Pfizer Inc.'s COX-2 inhibitor Bextra (valdecoxib) and F. Hoffmann-La Roche Ltd.'s acne drug Accutane (isotretinoin).

Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs, disagreed. "I do not have reason to believe that set of five drugs is specifically more concerning [than other drugs]," she said, according to The Associated Press.

Kweder's reassurance, however, may not comfort investors, according to Friedman, Billings, Ramsey & Co. analyst David Moskowitz. "David Graham was the FDA researcher who had questioned Vioxx's safety before it was recalled, so a list of drugs he's also concerned about is going to be taken quite seriously," Moskowitz speculated, according to TheStreet.com.

Investors Thursday most sharply reacted to the concerns regarding pharmaceutical brands Crestor and Serevent. Crestor has been associated with rhabdomyolysis—a muscle-wasting disease that prompted the recall of Bayer AG's statin Baycol (cerivastatin)--while Serevent has been linked with an increased risk of asthma-related death.

Shares of AstraZeneca closed at $40.34, down $3.80, or 8.6 percent, while GSK shares closed at $43.59, down $1.45, or 3.2 percent, both in heavy trading on Wall Street.

Monday, November 15, 2004

IN BRIEF: THE FOOD AND DRUG ADMINISTRATION

The Food and Drug Administration has planned an advisory panel meeting for Feb. 16 and 17 to discuss whether the heart problems observed with Merck & Co. Inc.'s Vioxx (rofecoxib) can be generalized to the entire class of COX-2 inhibitors. Dr. Curt Ferberg of the Wake Forest University School of Medicine had been invited to the meeting, but had his invitation rescinded after he presented a study of Pfizer Inc.'s Bextra (valdecoxib) at the American Heart Association meeting held last week, according to The Associated Press. Dr. Ferberg was told not to attend the meeting since he had already expressed his views in public. Ferberg reportedly said Bextra is as dangerous as Vioxx, and Pfizer is trying to suppress that information.

Monday, October 18, 2004

PFIZER WILL CONDUCT LONG-TERM CARDIOVASCULAR STUDIES OF BEXTRA, UPDATE LABEL TO REFLECT SKIN-REACTION RISK

Pfizer Inc. said Friday it plans to conduct long-term studies to examine the cardiovascular safety of its COX-2 inhibitor Bextra (valdecoxib) and is working with regulatory authorities to update the Bextra label to reflect the risk of a rare but serious skin reaction.

After Merck & Co. Inc.'s COX-2 inhibitor Vioxx (rofecoxib) was withdrawn from the market last month due to increased cardiovascular risk, Pfizer examined its clinical trial database for Bextra, which includes 8,000 patients treated for durations ranging from six to 52 weeks. Pfizer said the review indicated no increased risk of cardiovascular thromboembolic events in patients treated for osteoarthritis or rheumatoid arthritis.

However, data from two trials involving individuals undergoing coronary artery bypass graft surgery showed patients treated with Bextra (alone or in combination with Pfizer's experimental, injectable COX-2 inhibitor parecoxib) had an increased incidence of cardiovascular events. Separate studies in general surgery showed no increased risk of cardiovascular thromboembolic events. Pfizer emphasized that Bextra is not approved in the United States for use in any surgical setting.

Pfizer said it will conduct further studies to confirm the long-term cardiovascular safety profile of Bextra in patients who require chronic treatment for arthritis.

Additionally, Pfizer sent a letter to health care professionals to alert them of the risk of a rare but serious skin reaction with Bextra. Bextra's label has included information on the condition since its introduction in 2002. However, Pfizer said it will update the label to show that the risk of this condition is greater with Bextra than with other COX-2 inhibitors and that the risk is greatest during the first two weeks of Bextra therapy.

Pfizer also markets the COX-2 inhibitor Celebrex (celecoxib).

Shares of Pfizer dropped $0.56, or 1.9 percent, to close at $28.52 on the New York Stock Exchange.

Friday, October 15, 2004

REPORT FINDS 276,000 PATIENTS SWITCHED TO OTHER COX-2 INHIBITORS, NSAIDS IN FIRST WEEK AFTER VIOXX RECALL

According to a Verispan report, more than 276,000 patients switched to other COX-2 inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) in the first week following the Sept. 30 recall of Merck & Co. Inc.'s Vioxx (rofecoxib) arthritis therapy.

Of the 276,000 patients, 36 percent (more than 100,000 patients) switched from Vioxx to Pfizer Inc.'s COX-2 inhibitor Celebrex (celecoxib). Celebrex claimed approximately 21 percent of the total prescriptions in the arthritis market for the week ended Oct. 8, up 4 percent from the prior week.

Overall, there were more than 2.1 million arthritis prescriptions in the market. In the four weeks prior to the recall of Vioxx, there were approximately 1.9 million prescriptions.

Thirty-three percent of those patients who switched were prescribed Bextra (valdecoxib), a COX-2 inhibitor manufactured by Pfizer, while generic NSAIDs accounted for 17.6 percent of Vioxx patient switches. Boehringer Ingelheim GmbH and Abbott Laboratories' Mobic (meloxicam) accounted for 12 percent of Vioxx patient switches.

The report noted that the number of switches from other COX-2 inhibitors increased during the week compared with the prior week, as there was a 24 percent increase in switching from Celebrex and a 15 percent increase in switching from Bextra.

Monday, October 11, 2004

COX-2 MARKET GROWS DURING WEEK OF VIOXX RECALL AS CONSUMERS REPLACE SUPPLIES; PFIZER GAINS MOST MARKET SHARE

Verispan reported U.S. consumers purchased nearly 913,000 prescriptions for COX-2-specific inhibitors during the week ended Oct. 1--the week of the recall of Merck & Co. Inc.'s Vioxx (rofecoxib)--7 percent more than in the week ended Sept. 24. The number of new prescriptions exceeded 484,000, up 28 percent from the previous week.

"The increase in the COX-2 market makes sense because patients are immediately discontinuing Vioxx and are replacing their supply with comparable alternatives," said Verispan Chief Executive Officer Greg Porter.

Verispan projected that 162,125 new prescriptions during the week were product switches by former Vioxx users.

Thirty-eight percent of patients who switched from Vioxx purchased Pfizer Inc.'s Celebrex (celecoxib), 32 percent switched to Pfizer's Bextra (valdecoxib) and 10 percent switched to Abbott Laboratories and Boehringer Ingelheim Pharmaceuticals Inc.'s Mobic (meloxicam). Eighteen percent of Vioxx users switched to a generic, non-specific, nonsteroidal anti-inflammatory drug.

Overall Celebrex prescriptions increased 26 percent week-over-week to 451,511, Bextra prescriptions were up 32 percent to 294,260 and prescriptions of Mobic climbed 43 percent to 90,495.

Vioxx prescriptions fell only 37 percent--from 265,626 to 167,062--since the recall was announced on Sept. 30, one day before the end of the study period.

Friday, October 8, 2004

COX-2 INHIBITOR CLASS OF DRUGS SHOULD BE REVIEWED FOR CARDIAC SAFETY, RESEARCHERS SUGGEST; DRUG COMPANY SHARES FALL

Shares of several drug companies fell Thursday following an article released on Wednesday calling for a review of other members of the COX-2 inhibitor class of drugs beyond Merck & Co. Inc.'s Vioxx (rofecoxib) to evaluate whether they, too, pose an increased risk of cardiac problems. Also criticized in a related article was the lack of earlier appropriate action by the Food and Drug Administration with respect to the Vioxx situation.

The reports, which were published Oct. 6 on the Web site of The New England Journal of Medicine ahead of the Oct. 21 print edition, draw attention to the notion that the increased risk of cardiac events among Vioxx users, which led Merck to voluntarily withdraw the drug last week, may extend to the entire COX-2 inhibitor class of drugs.

"It is essential to determine whether the cardiovascular risk is or is not a class effect," wrote Dr. Garrett Fitzgerald, a cardiologist with the University of Pennsylvania School of Medicine.

In another article, cardiologist Dr. Eric Topol suggested the FDA's "passive position" of waiting for data to accrue is not acceptable "given the strong signals that there was a problem and the vast number of patients who were being exposed."

The only other Food and Drug Administration-approved drugs in this class that are currently available are Pfizer Inc.'s Celebrex (celecoxib) and Bextra (valdecoxib). Novartis AG's Prexige (lumiracoxib) is awaiting FDA approval.

Also on Wednesday, the European Medicines Agency said it would review all Pharmaceutical brands in this class in the wake of Merck's withdrawal of Vioxx.

However, Pfizer's medical director, Dr. Gail Cawkwell, said there is no evidence of increased risk of heart problems among the 75 million Americans who have taken Celebrex, according to The Associated Press.

Shares of Merck closed at $30.98, down $0.69, or 2.2 percent. Pfizer was down 3.8 percent, or $1.19, to close at $29.99. Novartis also fell to close at $45.49, a decrease of $1.19, or 2.6 percent. All the shares were heavily traded on the New York Stock Exchange.