Celebrex Warning
A SELF-IMPOSED BAN ON DRUG ADS
June 17, 2005
The New York Times
The drug maker Bristol-Myers Squibb said yesterday that it had imposed a ban on advertising its new drugs to consumers in their first year on the market, adopting voluntary restrictions that go further than what is anticipated in an industrywide advertising code to be announced next month.
The company said it wanted to give doctors time to understand new products before patients begin asking for them.
"We want to make sure that before we start mass media - television, radio and print branded advertising - that physicians have a level of comfort about the treatment and which patients are appropriate for it," Brian Henry, a spokesman for Bristol-Myers, said.
The 12-month ban is part of a new advertising code the company posted on its Web site yesterday.
Despite the growing backlash against direct-to-consumer advertising of pharmaceuticals, Mr. Henry said the company is not aware of any similar codes in the industry.
In the eight years since the Food and Drug Administration lifted a prohibition on consumer advertising, drug ads have become a $3.8 billion business. The constant drumbeat of spots, mostly on television, is so effective that patients demand prescriptions from their doctors, and some critics accuse the physicians of obliging even though the drugs might not be best for the patient.
The practice has become particularly controversial in the last year in the wake of disclosures that the prescription painkillers known as cox-2 inhibitors were linked to cardiac problems. Advertising and marketing played a role in the widespread use of two of the drugs, Vioxx and Celebrex, by many patients who would have done just as well with less expensive over-the-counter remedies, critics have said.
The Pharmaceutical Research and Manufacturers of America, the trade group, is expected to adopt its industrywide code next month, but apparently will stop short of embracing anything like the 12-month moratorium on advertising new drugs.
"We believe passionately that patients have a right to know about new drugs which may save their lives or improve the quality of their lives," said Ken Johnson, a spokesman for the trade group, known as PhRMA. Mr. Johnson said that the "finishing touches" were being put on the new code, but he would not divulge its contents.
The chief executive of Bristol-Myers, Peter R. Dolan, is slated to become chairman of the industry trade group next year. Mr. Dolan's company has been working to improve its image in the wake of investigations of its accounting practices by the Justice Department and the Securities and Exchange Commission.
Direct-to-consumer advertising became an issue in last year's presidential campaign, with the Democrats holding drug advertising partly responsible for ever-increasing prescription costs and inflation in the nation's health care bills. Lawmakers, both at the federal and state levels, have also embraced the issue.
One bill pending in Congress, sponsored by Representative James P. Moran, a Democrat from Virginia, would ban the broadcast of all erectile dysfunction ads from 6 p.m. to 10 p.m., a measure partly aimed at limiting the exposure to children of the suggestive content of ads for Viagra, Cialis and Levitra.
In addition to placing a 12-month moratorium on consumer advertising of new drugs, Bristol-Myers' code calls for advertising to "appropriate audiences at appropriate times of the day" - a section apparently influenced by ubiquitous erectile dysfunction advertising.
The code also said that all company ads will inform poor patients that assistance programs are available to help them get medications. Bristol-Myers is based in New York.
STUDY SHOWS HOW COX-2 DRUGS DAMAGE HEART
May 26, 2005
HEARTCENTER ONLINE
May 26 (HeartCenterOnline) - Researchers at University of Pennsylvania School of Medicine believe they have uncovered another link in the chain of events that causes COX-2 inhibitors to increase the risk of heart attack.
Until 2004, COX-2 inhibitors were some of the most heavily prescribed medications in the United States for the relief of pain and inflammation. In late 2004, however, a study linked Vioxx, a leading COX-2 inhibitor, to increased risk of heart attack. Vioxx was voluntarily removed from the market by its manufacturer. Since then, other COX-2 inhibitors have been linked to heart attack, and one more (Bextra) has also been voluntarily removed from the market.
The researchers at Penn looked at COX-2 inhibitors' effect on the muscular wall of blood vessels. They found that a COX-2-derived fatty acid called prostacyclin controls the blood vessel response to stressors such as high blood pressure. By inhibiting COX-2, the drugs impair the ability of blood vessels to react to high blood pressure.
Combined with earlier research, this study may help physicians understand why COX-2 inhibitors affect the heart and raise heart attack risk even among patients who were previously at low risk.
Other studies have shown that, by suppressing prostacyclin production, COX-2 inhibitors predispose people to high blood pressure, which aggravates atherosclerosis, a condition in which the arteries gradually become clogged with plaque deposits. When the additional factor of impaired blood vessel response is added, it may help physicians better understand, and therefore manage, this class of drugs.
BEXTRA AGREES TO SUSPEND SALES OF BEXTRA
April 7, 2005
Bloomberg.com
Pfizer Inc., the world's biggest drugmaker, agreed to suspend sales of its Bextra painkiller because of heart risks, the U.S. Food and Drug Administration said today.
Pfizer will add a warning to its other painkiller, Celebrex, highlighting the potential of increased cardiovascular risks, the agency said in an e-mailed statement. Similar prescription painkillers will have to carry the same warning. Older painkillers such as aspirin will have to carry cautions about the possibility of cardiovascular and gastrointestinal risks, the agency said.
The FDA went against the advice of a panel of doctors and scientists, which in February concluded that Bextra was beneficial enough to justify its continued sale. Pfizer said in a statement that it disagrees with the FDA's decision and will hold further discussions with the agency about returning Bextra to the market.
"They stood up and defended the product saying there were no side effects, now the FDA has withdrawn it and there is a likely threat of litigation,'' said Karl Heinz Koch, a drug analyst at Lombard Odier Darier Hentsch in Zurich. "There will certainly be an investigation as to whether or not there was any wrongdoing by Pfizer.''
Shares of New York-based Pfizer fell 86 cents, or 3.2 percent, to $26 as of 9:30 a.m. in New York Stock Exchange composite trading.
WARNINGS ON POPULAR PAIN KILLERS
March 23, 2005
CBS, Online
The American Heart Association is weighing in on the controversy surrounding the link between pain killers and heart problems, offering its own recommendations for patients taking prescription medications like Celebrex and Bextra.
Their recommendation is to use the drug with the fewest known risks, The Early Show medical correspondent Dr. Emily Senay explains. That's very important and that may vary from patient to patient. So you need to think very carefully about your individual patient and what their risk factors are. Then physicians should limit the usage.
The concern is that patients are overdoing it with pain medication. Most of these recent studies linking cardiovascular disease to pain killers have studied usage over a long period of time. And the findings indicate that the risk of suffering heart problems increases with the length of the usage. So you can keep the chances of experiencing cardiovascular problems by limiting your exposure and taking a low dosage.
While studying the possibility that Celebrex and Bextra might be beneficial in cancer prevention, researchers saw an increased risk for heart problems. Two different studies - one from Brigham and Women's Hospital and Harvard Medical School and another from the Texas Heart Institute - found patients who took these drugs had an increased chance of suffering a heart attack or other cardiovascular problem.
And back in February, an advisory panel for the Food and Drug Administration ruled that the painkillers are believed to pose an increased risk for heart problems. But they claim that the benefits outweigh the dangers and therefore the drugs should stay on the market. A third drug, Vioxx, was taken off the market voluntarily by its manufacturer in September of 2004.
The American Heart Association is not saying to avoid these medications at all costs, but they do recommend searching for a safer alternative before relying on Celebrex or Bextra for pain relief.
The first choice should be to try an over-the-counter pain reliever such as aspirin, acetaminophen, or ibuprofen. They are proven to be safe and effective for pain relief. But again, you need to ask you doctor about which ones are right for you.
Every drug has side effects, and you need to pay attention to the directions and take the doses recommended by the manufacturer. Remember, aspirin is widely recognized for its protective benefits when it comes to heart disease. That's becase of its blood-thinning qualities that help prevent the clogging of arteries. Low doses of aspirin already are widely prescribed to prevent heart attack or stroke in people who already have cardiovascular problems.
The American Heart Association says physicians really need to keep in mind the risk factors associated with Celebrex and Bextra. In addition to the patient, doctors should also be looking for safer alternatives and should weigh the benefits and risks before prescribing Celebrex or Bextra.
FDA PANEL SAYS CELEBREX SHOULD STAY ON THE MARKET
February 18, 2005
The New York Times
A federal drug advisory panel today overwhelmingly recommended that Celebrex, the popular Pfizer pain reliever, should remain on the market, despite risks it poses to the heart. The panel also said that Bextra, a newer Pfizer pain reliever, carries increased cardiovascular risks, but it was still discussing whether to recommend that Bextra remain on the market.
Virtually all the panel's 31 members agreed that the possible benefits from Celebrex outweighed the chances of cardiovascular problems. But there was debate over how restricted the drug's use should be. Some committee members suggested that all cox-2 drugs should be "last resorts," while others disagreed or quibbled over what "last resort" means. In the end, most of the panel members agreed that Celebrex should carry a "black box" warning, the strongest used for prescription drug.
The panel's recommendations came during the last of three days of hearings at which panel members said they believed that all the cox-2 drugs - which include Vioxx, Bextra and Celebrex - carried heart risks.
In December, the Food and Drug Administration said in a statement that data showed higher cardiovascular risks for patients taking 400 milligrams or 800 milligrams a day of Celebrex, and it advised physicians who continued to prescribe Celebrex to choose "the lowest effective dose of Celebrex." The company says that Celebrex is available in 100- and 200- milligram capsules, as well as 400 milligrams.
Shares of Pfizer this afternoon were trading up 65 cents, or 2.6 percent, at $25.71.
The panel's assessment of Celebrex and Bextra today came just a day after a top research official at Merck, which makes Vioxx, suggested to the federal drug advisory panel that the company might soon decide to resume selling its painkiller in the United States.
The Merck official, Dr. Peter Kim, said that if the panel decided that Celebrex and Bextra, drugs similar to Vioxx, also hurt the heart, "then that would be important to us to take that into consideration with regard to Vioxx."
Dr. Alastair Wood, the chairman of the advisory panel reviewing drugs in a class known as cox-2, asked Dr. Kim what he meant. "Are you saying that if we think that the cardiovascular risk is a class effect, then you would consider putting Vioxx back on the market?" Dr. Wood asked.
Dr. Kim did not answer directly, but said: "The science has progressed. There are unique benefits to Vioxx."
In a statement, Merck said, "If the advisory committee and the F.D.A. conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers."
Dr. Paul Seligman, a top F.D.A. official, said it was too early to determine how the agency would respond if Merck sought to resume Vioxx sales.
The news was a remarkable disclosure in an already landmark hearing. Panel members have been sifting through studies trying to weigh the risks and benefits of Vioxx, Celebrex and Bextra. None of the drugs cure pain any better than older medicines. They were developed with the hope that they would cause fewer ulcers than older medicines, but Merck withdrew Vioxx in September after a study showed that the drug doubled the risks of heart attack and stroke.
Since then, more studies have shown similar risks for Celebrex and Bextra. The agency called the committee together to tell it what to do. According to much of the testimony, the committee will probably suggest that the drugs stay on the market, with tough warnings about the risks of taking them.
"I don't think any one of us is saying that these drugs should be taken off the market but that they should be used at the lowest safest dose," said Dr. Gary Hoffman of the Cleveland Clinic.
Dr. Michael Domanski of the National Institutes of Health agreed, saying, "It's pretty clear that there is an excess risk confirmed by some or all of these drugs."
The problem, many committee members said, is that patients who are at high risk of developing ulcers are often the same ones who are at risk of heart attacks.
"Finding the sweet spot for these drugs becomes a little bit harder," said Dr. Steven Nissen, a panel member from the Cleveland Clinic. "Older people are at greater risk for gastrointestinal bleeding, and I can assure you that they are greater risk for coronary disease."
February 17, 2005
The Associated Press
A Merck & Co. official said Wednesday that all painkillers in the same class as the company's Vioxx could cause heart problems or strokes, a change from the drug-maker's earlier position that such health issues appeared limited to its drug.
Dr. Ned S. Braunstein, senior director of Merck Research Laboratories, told two panels of Food and Drug Administration advisers that since the company pulled Vioxx from the market last year, studies suggesting similar problems with Celebrex and Bextra have changed his mind.
"The data strongly suggest it is a class effect," for all drugs of that type, Braunstein said.
The drugs, designed to help people in chronic pain from conditions such as arthritis, are known as Cox-2 inhibitors. At least two other Cox-2 drugs are awaiting approval from the FDA, Arcoxia from Merck and Lumiracoxib from Novartis Pharmaceuticals.
The panels plan to discuss those drugs Thursday.
The two advisory committees are holding a joint three-day session to gather data on the safety of Cox-2 drugs and to make recommendations regarding their future use.
Recommendations could range from limiting these drugs to people not known to be at risk of heart problems, reducing the dose or duration of use, requiring tougher warning labels and even taking the drugs off the market.
Merck pulled Vioxx off the market Sept. 30 after a long-term study showed a higher rate of strokes and heart problems in people using the drug.
A panel of federal judges on Wednesday assigned all pending Vioxx product liability lawsuits against Merck to Judge Eldon E. Fallon in Louisiana, who is experienced in major pharmaceutical litigation.
There were preliminary indications of heart problems with the painkiller Vioxx before it was withdrawn, but it was difficult to sort through conflicting data, a health official said Wednesday at the opening of hearings on the risks of popular painkillers.
"We were not asleep at the wheel, we were actually engaged in reviewing a lot of data," Dr. Lourdes Villalba told a joint meeting of the FDA's arthritis advisory committee and its drug safety and risk management advisory committee, which are looking into Vioxx, Celebrex and Bextra.
CBS News Early Show Medical Correspondent Dr. Emily Senay reports the hearings are an attempt to answer why these drugs ended up on the market in the first place.
"How was it that risk factors for cardiovascular events like stroke and heart attacks, which were clearly there in some of the early studies, were not taken more seriously?" Senay asked. "These drugs were better than approved by the FDA, and yet, we're at the place in time when we're questioning whether or not they should be on the market."
Related drugs Celebrex and Bextra, made by Pfizer Inc., remain on the market, though some studies have also indicated they, too, may carry an added heart risk.
Villalba, medical officer responsible for Vioxx at the FDA's Center for Drug Evaluation and Research, pointed out that a study done in 2000 comparing Vioxx with the painkiller naproxen, showed a higher rate of heart problems with Vioxx, but other studies had conflicting results. In discussions with Merck officials, she said, the company suggested naproxen might have a heart protective effect.
Nonetheless, in 2002 the agency required an added warning on the Vioxx label urging caution in prescribing it for people with heart conditions.
"We never bought the naproxen theory," she said, and Merck officials said they no longer make that argument.
Pfizer vice president Dr. Joseph M. Feczko said the reports of increased heart problems need to be seen in context, considering that these drugs, known as Cox-2 inhibitors, bring an important benefit by reducing the sometimes serious stomach and intestinal problems that occur with many painkillers.
Dr. Kenneth M. Verberg, Pfizer vice president for inflammation and immunology, defended Celebrex as safe, though he said there is little data on use of the drug for more than one year. Further long-term testing of Celebrex is needed, he said.
Earlier, Dr. Ned S. Braunstein, senior director of Merck Research Laboratories, reported that the biggest increase in heart problems occurred after 18 months of use.
Earlier in the day, Dr. Garrett FitzGerald of the Department of Pharmacology at the University of Pennsylvania School of Medicine told the committees that, considering the hazard reports, similar new drugs may have to face tougher testing to win approval and those on the market ought to be put through the same new testing to retain approval.
FitzGerald told the panels that, just as low-dose aspirin affords heart protection and a small but definite risk of stomach and intestinal problems, so the Cox-2 inhibitors "afford gastrointestinal protection and a small but absolute risk of cardiovascular events."
CBS' Aleen Sirgany reports, FitzGerald said: "We're likely to subject new drugs in this class to hurdles before they're approved. Existing drugs should be subject to the same hurdles."
The two committees are holding a joint three-day session to gather data on the safety of the drugs and to make recommendations regarding their future use.
Recommendations could range from limiting these drugs to people not known to be at risk of heart problems, reducing the dose or duration of use, requiring tougher warning labels and even taking the drugs off the market.
As the session began, the FDA promised prompt action on recommendations from advisory committees.
Dr. Steven Galson, acting director of FDA's Center for Drug Evaluation and Research, reminded the committees that the drugs in question are important painkillers widely used by people in chronic pain. It is important to balance the risks of drugs with their benefits, he said.
A drug that has a positive risk-benefit balance for the population as a whole, Galson added, may still cause serious problems for some individuals.
The FDA has been criticized for being slow to recognize problems with these drugs.
However, committee chairman Dr. Alistair J. Wood of Vanderbilt University stressed as he opened the session that the committee "is not here to delegate blame or revisit the past."
On Tuesday, the Health and Human Services Department announced that the FDA will establish a new Drug Safety Oversight Board to monitor medicines once they're on the market and will update physicians and patients with emerging information on risks and benefits.
The Health and Human Services Department announced Tuesday that the FDA will establish a new Drug Safety Oversight Board to monitor medicines once they're on the market and will update physicians and patients with emerging information on risks and benefits.
But as CBS News Correspondent Sharyl Attkisson reports, skepticism exists • even within the FDA • over whether such a drug review panel will work.
Attkisson spoke with FDA Dr. David Graham, who recently studied such drugs as Celebrex and Mobic, an alternative pain medication, with a doctor at Stanford University. Graham said his and other similar studies are not only not being encouraged by the FDA, but they are being withheld from the public.
Graham has been critical of the FDA before, alleging it repeatedly kept the public in the dark over potentially dangerous drugs. He said if the FDA worked in the public interest, it would encourage him to present his study.
"You would think that if the FDA were working for the public and were interested in drug safety that that would be their reaction," Graham told Attkisson.
February 7, 2005
The Chicago Tribune
When the painkiller Mobic entered the market five years ago, it was the Rodney Dangerfield of prescription arthritis treatments.
At the time, painkillers Vioxx and Celebrex were in the spotlight, billed as new drugs that didn't tatter stomach linings like their predecessors. Mobic was also new to market but was merely the newest in an old class of drugs that can upset stomachs.
Unable to share the stage of the new "Cox-2 inhibitors," Mobic's maker competed on price, launching the drug at 40 cents a pill less than its better-known rivals.
"If you can bring the price in a little lower in order to make it more accessible to more patients, it's going to be more successful," Mobic's maker said at the time.
But how times have changed.
Mobic is finally getting some respect and has, in fact, become the most frequently prescribed brand name--and often the most expensive--since reported health risks prompted Vioxx's maker to pull it from the market and warnings were circulated about Celebrex.
Mobic's price has shot up substantially--77 percent since 2002 for its 15 milligram tablet and 38 percent for its 7.5 mg pill--far outpacing inflation and running counter to smaller annual increases more common in the drug industry.
Just last month, maker Boehringer Ingelheim raised the average wholesale price of each tablet to $4.61 for a 15 mg pill and $3.26 for a 7.5 mg dose, which are respective increases of 11 percent and 7 percent, industry price guides show.
The commonly prescribed dose of Celebrex, a 200 mg pill, costs $3.26.
Just three years ago, when Cox-2s were the most commonly prescribed brand-name painkillers, Mobic's tablets were $2.35 for the lower dose and $2.59 for the higher, compared with $2.87 for a 200 mg Celebrex. That 28-cent to 52-cent per pill difference costs consumers without drug coverage an additional $100 to $200 a year.
Mobic's price increases buck the party line often taken by drugmakers who claim they reap profits on sales volume rather than price increases.
In this case, Mobic's distributors, including North Chicago-based Abbott Laboratories, are generating revenues and profits on both. This is dismaying to consumer groups and health insurers, who say the companies never would have achieved such sales if not for the controversies surrounding Cox-2 drugs.
"The most generous thing I can say is that this is exploitation of the public," said Dr. Sidney Wolfe, director of the Health Research Group at consumer group Public Citizen.
The price hikes, coupled with increased usage in the wake of the controversies surrounding Cox-2s, has been a boon to the co-marketers of Mobic--Abbott and German-based Boehringer.
4th-quarter U.S. sales up 177%
Abbott last month reported a 177 percent gain in U.S. sales of Mobic, to $258 million, in the fourth quarter, putting the drug on track to reach blockbuster status this year by achieving annual U.S. sales of more than $1 billion. Last year, its sales were $593 million.
Neither company would disclose Mobic's profits.
For its part, Abbott is distancing itself from the pricing of Mobic, saying "the decision regarding Mobic price was made by Boehringer Ingelheim."
Boehringer acknowledged the price hikes were its idea, saying the pricing was planned well before Vioxx was pulled. In addition, the company said the ramp-up in prices in recent years was needed due to an unusually short time to recoup development costs.
"We had a limited period of exclusivity to recapture an investment in this product," said Paul Fonteyne, executive vice president of sales and marketing at Boehringer.
"The price of the product ... predates the unfortunate situation that plagued the Cox-2s," he said.
Unlike most drugs approved in the United States that have 20-year patent protection, Boehringer said Mobic didn't get that. The FDA in 2000 granted Mobic five years of exclusivity.
Price plan not new, firm says
Fonteyne said the pricing strategy has not changed since the drug was launched.
"We had planned to get to a point where we had some parity with Celebrex [pricing]," Fonteyne said, arguing that some arthritis sufferers who take Celebrex could still see a price break if they switch to Mobic.
Fonteyne claims 37 percent of arthritis sufferers who take the 200 mg dosage of Pfizer Inc.'s Celebrex take it twice a day, so the two-pill regimen, a total of 400 mgs, would end up costing patients more than either Mobic dosage, he said, citing industry market research.
Pfizer, however, says the recommended dose of Celebrex is of 100 mg to 200 mg daily for osteoarthritis. Meanwhile, some doctors say it's common to prescribe a two-pill regimen of 7.5 mg Mobic.
Regardless of the dosing, any time drugmakers raise their prices, health insurers and benefits analysts say such increases are almost always passed along to employers and consumers.
"When the prices of any given drug go up, if an employer's benefit plan is a co-payment plan, then the employer absorbs 100 percent of that price increase," said Bridget Eber, pharmacy practice leader for employee benefits consultancy Hewitt Associates of suburban Lincolnshire.
"If the employer's plan is a co-insurance plan, then the price increase is absorbed by both the employer and the employee. Both are paying a percentage of the covered charge," Eber said.
Effectiveness questioned
As for Mobic, critics like Wolfe say the drug is no more effective than older non-steroidal anti-inflammatories that are "much less expensive."
Ironically, the stomach safety of Celebrex has since been discredited because the drug has not been able to win U.S.-approved labeling that touted gastrointestinal benefits over the widely used class of non-steroidal anti-inflammatory drugs that includes Mobic, ibuprofen and other common remedies that have well-known stomach issues, particularly for long-term use.
Mobic's safety may come under question, too.
It may be among the arthritis medications that will be discussed later this month during a high-profile FDA hearing to discuss Cox-2 drugs and "related medicines," federal regulators said.
Two FDA committees will discuss "benefit-to-risk considerations" of painkillers, featuring Cox-2s and cardiovascular and gastrointestinal concerns about such drugs.
CONSUMER GROUP SAYS 1999 STUDY OF PFIZER'S DRUG REVEALS HEART HAZARDS
February 7, 2005
Chemical & Engineering News
Consumer advocacy group Public Citizen confronted Pfizer last week over a 1999 study of the drug firm's COX-2 inhibitor Celebrex, claiming that the company has been sitting on unfavorable results. The challenge is one of the first stemming from postings on newly launched clinical trial websites.
Pfizer acknowledges that patients taking Celebrex in the trial involving 425 patients--performed to assess the drug as a treatment for Alzheimer's disease--suffered heart attacks at nearly four times the rate of patients taking placebos.
The company counters, however, that information on the study has been public since 2000. Pfizer also claims that it is not possible to draw clinically meaningful conclusions from the study alone, given variations in patients' medical history. As recently as last October, Pfizer claimed that no completed study of Celebrex had pointed to increased heart risks.
The confrontation comes two weeks before an FDA conference on COX-2 inhibitors, a class of drugs that has been at the center of calls for more public information from clinical trials on drug safety.
Last month, Public Citizen petitioned FDA to ban COX-2 inhibitors on the basis of clinical data that had come to light indicating health risks for several drugs in the category. Sydney M. Wolfe, director of Public Citizen's health research group, says information recently posted on an industry-sponsored website about Pfizer's Celebrex trial supports his group's contention that the drugs are unsafe and that drug companies have suppressed results.
"Public Citizen's cherry-picking of data is alarmist and misconceived," says Joseph M. Feczko, president of worldwide development at Pfizer. Feczko adds that an independent panel monitored the study and that an abstract was presented at a scientific congress in Stockholm in 2000. Wolfe tells C&EN that the conference abstract was a "whitewash" that did not include the negative results that Pfizer posted on the website.
Observers say the confrontation illustrates the potential for confusion as the public gains access to difficult-to-interpret data.
According to Michael A. Valentino, chief consultant for pharmacy benefits management at Veterans Health Administration (VHA), interpreting clinical trial data is a problem even for medical researchers. "For every study that shows harm, you can find two that don't. And vice versa," Valentino says. "You really need to dig a lot deeper."
VHA looks to FDA for guidance, he says. "But we don't stop there. We do our own evaluation and critiques of published studies and, more importantly, we look at experience in our own patient population."
Valentino says VHA is still prescribing and dispensing Celebrex. Meanwhile, managed care giant Kaiser Permanente says it will stop dispensing Pfizer's other COX-2 drug, Bextra (valdecoxib), pending further evaluation of the drug's safety.
US URGES LIMITING USE OF CELEBREX
December 23, 2004
Reuters
WASHINGTON -- U.S. health regulators recommended on Thursday that doctors limit prescribing painkillers like Pfizer Inc.'s Celebrex and Bextra, in light of recent evidence that they may increase the risk of heart attack and stroke.
A Food and Drug Administration health advisory said officials were still weighing sometimes conflicting data, urged physicians to consider the recent information in weighing the benefits and risks for individual patients.
"The actions that we're recommending in the advisory are for more limited prescribing than would currently be included in the approved labeling for these products," John Jenkins, director of the FDA's Office of New Drugs, told reporters on a conference call.
Patients vulnerable to gastric bleeding associated with older painkillers may still be appropriate candidates for Cox-2 drugs that include Celebrex and Bextra, the FDA said.
A Pfizer representative was not immediately available to comment on the FDA advisory.
The FDA action follows a recent series of warnings of increased heart attacks and strokes connected to both over-the-counter and prescription painkillers.
Merck & Co. Inc. voluntarily withdrew its arthritis drug Vioxx in September after a study showed the painkiller doubled the chances of heart attacks and strokes.
Pfizer has kept arthritis medicine Celebrex on the market, but agreed this week to suspend consumer advertising. Pfizer has also placed a new note on its Bextra painkiller, warning of increased heart attacks and blood clots in patients who have just had heart bypass surgery.
Health officials warned on Monday of a risk of heart attack and stroke in over-the-counter naproxen, sold as a generic and as several brand names, including Bayer AG's Aleve, and as Roche AG's Naprosyn.
Vioxx, Celebrex and Bextra are in a newer class of painkillers known as COX-2 inhibitors, designed to avoid the gastric bleeding associated with older drugs like aspirin.
COX-2 inhibitors, in turn, are a subset of a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), which include aspirin, naproxen and ibuprofen.
WASHINGTON (Reuters) - Pfizer Inc. has agreed to suspend its advertisements for arthritis drug Celebrex while U.S. regulators review new data that link the drug to an elevated risk of heart attacks, a Food and Drug Administration spokeswoman said on Sunday.
The FDA asked the drug giant on Friday night to temporarily cease the Celebrex ads, and the company agreed, FDA spokeswoman Kathleen Quinn said. Celebrex has been heavily promoted in television commercials and magazine ads, helping propel sales of the drug to nearly $2 billion last year.
The FDA also is working with Pfizer "to develop appropriate information for physicians" about the new findings, Quinn said.
Pfizer could not immediately be reached for comment on Sunday night.
Earlier Sunday, Pfizer Chief Executive Hank McKinnell said doctors should be made aware of the health risks in prescribing Celebrex to their patients, but the company did not plan to recall the popular arthritis drug.
"We're leaving Celebrex on the market because it is an appropriate option for many, many patients," McKinnell said on ABC's "This Week." "Physicians do need to be fully advised of the risks and particularly this new information."
On Friday, Pfizer said Celebrex more than doubled the risk of heart attack in a large cancer-prevention trial, a setback that came just weeks after Merck & Co. recalled its similar Vioxx drug due to heart safety risks.
The FDA on Friday urged doctors to consider prescribing alternatives to Celebrex. The agency said it was leaving all regulatory options open and would have more announcements about Celebrex in the next few days.
Dr. David Graham, associate director for science in the FDA's Office of Drug Safety, criticized the agency for failing to protect the public from dangerous drugs.
"The FDA, I believe, is more concerned with getting drugs on to the market than it is in getting safe drugs on to the market," Graham said on the same television program.
Merck recalled Vioxx on Sept. 30 after a study found that a long-term use of the drug doubled the risk of heart attack and stroke. Both Celebrex and Vioxx belong to a class of drugs known as COX-2 inhibitors. They work by selectively blocking a protein called COX-2 that has been linked to inflammation.
The FDA said on Friday it had serious concerns about the whole range of COX-2 inhibitors, which includes another Pfizer drug called Bextra.
Pfizer said the Celebrex trial, sponsored by the National Cancer Institute, involved patients taking 400-milligram and 800-milligram daily doses of the drug to prevent tumors known as adenomas that grow from glandular tissue. High doses of the anti-inflammatory drug were being tested on the theory that inflammation is a cause of cancer.
Celebrex is one of Pfizer's biggest products, with 2003 sales of $1.9 billion.
December 19, 2004
Reuters
WASHINGTON -- Pfizer Chief Executive Hank McKinnell said on Sunday doctors should be made aware of the health risks in prescribing Celebrex to their patients, but the company does not plan to recall its popular arthritis drug.
Pfizer Inc. on Friday said Celebrex more than doubled the risk of heart attack in a large cancer-prevention trial, a setback that comes just weeks after Merck & Co. recalled its similar Vioxx drug due to heart safety risks.
"We're leaving Celebrex on the market because it is an appropriate option for many, many patients," McKinnell said on ABC's "This Week." "Physicians do need to be fully advised of the risks and particularly this new information."
The Food and Drug Administration on Friday urged doctors to consider prescribing alternatives to Celebrex. The agency said it would have more announcements about Celebrex in the next few days.
Dr. David Graham, associate director for science in the FDA's Office of Drug Safety, criticized the agency for failing to protect the public from dangerous drugs.
"The FDA, I believe, is more concerned with getting drugs on to the market than it is in getting safe drugs on to the market," Graham said on the same television program.
Merck recalled Vioxx on Sept. 30 after a study found that a long-term use of the drug doubled the risk of heart attack and stroke. Both Celebrex and Vioxx belong to a class of drugs known as COX-2 inhibitors. They work by selectively blocking a protein called COX-2 that has been linked to inflammation.
Pfizer said the Celebrex trial, sponsored by the National Cancer Institute, involved patients taking 400-milligram and 800-milligram daily doses of the drug to prevent tumors known as adenomas that grow from glandular tissue. High doses of the anti-inflammatory drug were being tested on the theory that inflammation is a cause of cancer.
Celebrex is one of Pfizer's biggest products, with 2003 sales of $1.9 billion.
December 19, 2004
Reuters
LONDON -- U.S. regulators have "serious concerns" about painkilling drugs in the class known as COX-2 inhibitors and are due to issue a new ruling on them within days, the Financial Times reported on its Web site on Sunday.
Lester Crawford, Acting Food and Drug Administration Commissioner, told the paper in an interview that the agency's review could result in the withdrawal of the entire range of drugs.
"We are looking at all the COX-2s and will make an announcement shortly," Crawford was quoted as saying by the FT. "All the regulatory options are open, including withdrawal. I have serious concerns about COX-2s as a class."
His comments came after U.S. health officials on Friday urged doctors to consider prescribing alternatives to Pfizer Inc.'s arthritis drug Celebrex while regulators examine new data on heart risks.
Celebrex is part of the same family of drugs as Merck & Co Inc.'s Vioxx which the company pulled from the market on Sept. 30 because it raised the risk of heart attack and stroke.
Regulators could ask Pfizer to pull Celebrex from the market although Pfizer has said it would fight any attempt to withdraw the drug.
"We find no basis for withdrawal" of Celebrex, Hank McKinnell, Pfizer chief executive, told the FT.
Also on Friday, the National Institutes of Health halted a trial testing Celebrex for cancer prevention because the drug more than doubled heart-attack risk compared with placebo.
The NIH said it was reviewing all government grants for studying Celebrex and other COX-2 inhibitors.
Celebrex and other similar drugs were designed to relieve pain with a lower risk of life-threatening stomach bleeding than older, over-the-counter drugs.
December 17, 2004
Associated Press
NEW YORK -- Celebrex, the nation's leading arthritis painkiller, raises the risk of heart attack when taken at very high doses, the drug's maker said today in the latest blow to a class of powerful and widely touted drugs.
Pfizer Inc. said it would not pull the drug from the market, but a study testing it for cancer prevention was halted. Some doctors said people should stop taking that medicine and others like it, called cox-2 inhibitors, until their safety is more thoroughly studied.
The Celebrex warning comes just two months after its one-time competitor, Vioxx, was pulled from store shelves for the same concerns.
"We thought Celebrex was safe and the problem was just with Vioxx," said Dr. Richard Hayes, a New York cardiologist who is recommending his patients switch from Celebrex to nonprescription medicines such as Advil to treat pain. "The problem is more complex than we thought."
The disclosure, which came from a study of Celebrex as a cancer prevention drug, sent Pfizer's shares tumbling because of fears that it could cripple sales of what had been the most-prescribed drug for treating arthritis.
The drug industry has already been under fire for numerous high-profile debacles: Merck & Co.'s withdrawal of Vioxx the failure of Chiron Corp. to deliver half the country's flu vaccines, and disclosures that drug companies had stifled negative clinical trial data from studies examining antidepressant use in children.
Anti-inflammatory drugs like Celebrex and Vioxx have been heavily advertised by the pharmaceutical industry as being more effective and less irritating to the stomach than some other pain relievers. And many scientists had high hopes for the drugs as cancer prevention medicines as well.
But Vioxx was pulled from the market in late September because it doubled patients' risk of heart attack and strokes -- a discovery made in a study of colon cancer patients. Scientists had hoped the drug would help prevent recurring polyps.
In the case of Celebrex, the National Cancer Institute suspended the use of the drug after discovering that patients taking the largest doses -- 400 to 800 milligrams a day -- had a 2.5 times greater risk of major heart problems. That study, too, was intended to test Celebrex's ability to prevent precancerous polyps in patients that lready had at least one such growth.
A separate cancer study found no increased heart risk with patients taking 400mg of Celebrex per day. The highest recommended dose for Celebrex to treat rheumatoid arthritis is 400mg, while the dose for osteoarthritis patients is 200mg a day.
Dr. Joseph Feczko, president of worldwide development for Pfizer, said the heart risk results were not consistent with a second long-term cancer prevention trial or with a "large body of data" the company had collected.
Given recent heavy criticism about the timeliness of Merck's disclosures about Vioxx, Pfizer seemed to rush out the news of the cancer institute findings. Pfizer chairman Henry McKinnell said in a statement the company wanted to "rapidly communicate new information to regulators, physicians and patients around the world."
Feczko said in an intervew later in the day that sales of Celebrex will continue because "it has not shown in totality that it increases the risk of heart attacks." He added that the company was still planning to go ahead with a previously announced study to see if Celebrex could actually help patients at high risk of heart attacks.
For the first nine months of the year, worldwide sales of Celebrex more than doubled from a year earlier to $2.3 billion, accounting for 6 percent of Pfizer's total sales of $37.6 billion during that period.
Barbara Ryan, a managing director at Deutsche Bank, said she expects Celebrex's sales to fall by 50 percent next year.
"In this environment people are hysterical," said Ryan.
Dr. Marie Griffin, an epidemiologist and drug safety expert at Vanderbilt University, said that while the Celebrex findings suggest that all cox-2 drugs have similar risks, the safety concerns may only apply to patients taking Celebrex at high doses.
Griffin and two other Vanderbilt epidemiologists also raised fresh concerns about Bextra, in a letter to be published Thursday in the New England Journal of Medicine. Doctors should not prescribe the drug "except in extraordinary circumstances," they recommend.
Still, some doctors are concerned about the drug at lower doses because different patients metabolize drugs at different rates.
"You can't say as a result of this study that doses under 400 milligrams are absolutely safe," said Dr. Eric Matteson, a professor of medicine in the division of rheumatology at the Mayo Clinic in Rochester, Minn.
Matteson said his office has been besieged with calls and that he plans to review his patients' records and take some of them off the drug. Some have asked for alternatives.
The withdrawal of Vioxx, another blockbuster drug, has been a financial and public relations disaster for Merck. Its legal liabilities are estimated at up to $18 billion.
Earlier this month, the Food and Drug Administration said it was adding a warning to the labels of another Pfizer drug, Bextra, noting a risk of potential heart problems associated with its use in people who have recently had heart bypass surgery. Bextra is also a cox-2 inhibitor.
Shares of Pfizer plunged $3.30, or 11.39 percent, to $25.68 in late afternoon trading on the New York Stock Exchange. The decline wiped out more than $25 billion of Pfizer's market value.
Also on Friday, Eli Lilly & Co. said it is warning doctors to stop using its attention deficit disorder drug Strattera in patients with jaundice or laboratory evidence of liver injury. Lilly said it was putting a boldface warning in the prescribing information that it gives doctors about the drug after two patients on the medication developed liver problems.
December 17, 2004
CNN
WASHINGTON -- With a new study that indicates the nation's leading arthritis painkiller could raise the risk of heart attacks, the Food and Drug Administration advised doctors Friday to consider "alternative therapy" to Celebrex.
Earlier Friday, drug giant Pfizer Inc. said it had no plans to pull the painkiller off the market despite the data that showed patients using the drug in a long-term cancer study had increased cardiovascular risks.
The FDA will look at the study results and would then "determine the appropriate regulatory action," the agency said in a news release.
The FDA said it advises doctors to evaluate "alternative therapy. At this time, if physicians determine that continued use is appropriate for individual patients, FDA advises the use of the lowest effective dose of Celebrex."
Celebrex is approved in the United States for treatment of osteoarthritis and pain at doses of 100 milligrams to 200 milligrams a day, or double that for rheumatoid arthritis. It was approved by the FDA in 1998 and has been prescribed to 27 million Americans, according to Pfizer.
Patients in the cancer study were taking 400 milligrams to 800 milligrams of Celebrex daily or placebos, Pfizer said in a news release. Compared with placebo users, the risk of heart trouble was 2.5 times greater for patients taking 200 mg of Celebrex twice daily and 3.4 times greater for those who took 400 mg twice daily.
About 3,600 patients took part in the five-year study, the release said.
Pfizer said a second cancer study that it funded found no problems, and a third is in progress.
Celebrex was expected to generate about $5 billion in sales for Pfizer next year, or about 9 percent of the company's total revenue, Sena Lund, an analyst for Cathay Financial in New York, had estimated before the announcement Friday.
Pfizer CEO Hank McKinnell told CNN the results from clinical trials were "unexpected," and said the company is taking "immediate steps to fully understand the results and rapidly communicate new information to regulators, physicians and patients around the world."
"We do know from a wealth of other information ... that Celebrex when taken as recommended, at the doses recommended, is safe and effective," he said.
Separately, New York-based Pfizer is facing an investigation by the New York attorney general's office related to Celebrex, a source familiar with the situation told CNN. The source said the probe was not linked to Friday's announcement but rather focused on claims of the effectiveness of the drug.
An official at New York Attorney General Eliot Spitzer's office declined to comment.
The FDA release said another Pfizer painkiller, Bextra, has been shown to increase risks of heart problems after bypass surgery.
Celebrex and Bextra were developed by Pfizer's Pharmacia division, which the company acquired in 2002.
December 17, 2004
Associated Press
NEW YORK -- Pfizer Inc. says it has found an increased risk of heart attacks with patients taking its top-selling painkiller Celebrex, a drug that is in the same class as Vioxx, which was pulled from the market in September because of safety concerns.
Pfizer announced Friday that it found the increased risk in one of two long-term cancer prevention trials, while the other trial showed no increased risk.
The National Cancer Institute, which was conducting the study for Pfizer, suspended the use of Celebrex after finding that patients taking 400mg to 800mg of the drug daily were found to have a risk of 2.5 times greater of experiencing major heart problems than those who weren't. A separate cancer study found no increased heart risk with patients taking 400mg of Celebrex per day.
Pfizer was conducting the trials as part of an effort to find a new application for the drug.
The news sent the stock of the giant pharmaceutical maker plunging in morning trading on the New York Stock Exchange, where its shares were down $4.14, or more than 14 percent, at $24.84 in heavy volume.
Both Celebrex and [Vioxx,](http://www.vioxxdrugrecall.com) which is made by Merck & Co., are a type of drug called cox-2 inhibitors, which have become popular because of their effectiveness in treating the pain of arthritis and other ailments.
Celebrex is the most-prescribed drug for treating arthritis. In the nine months ending in September, worldwide sales of Celebrex more than doubled from the same period a year earlier to $2.29 billion, accounting for 6 percent of Pfizer's total income of $37.59 billion.
Pfizer did not indicate that it was withdrawing Celebrex from the marketplace.
The withdrawal of Vioxx has been a financial and public relations disaster for Merck. Its legal liabilities are estimated at up to $18 billion, and its shares have dropped by nearly one-third since the recall announcement was made in late September.
Vioxx had been a blockbuster drug for Merck, it's No. 2 earner with annual global sales of $2.5 billion, amounting to 11 percent of the company's $22.49 billion in revenue last year. Some 2 million people worldwide had been taking Vioxx.
Dr. Joseph Feczko, president of worldwide development for Pfizer, noted that the results in the trial finding increased risk of heart attacks were not consistent with either the other cancer prevention trial or with a "large body of data" that the company had collected.
"Pfizer is taking immediate steps to fully understand the results and rapidly communicate new information to regulators, physicians and patients around the world," Pfizer's chief executive Hank McKinnell said in a statement
Earlier this month, the Food and Drug Administration said it was adding a warning to the labels of another Pfizer drug, Bextra, noting a risk of potential heart problems associated with the use of Bextra in people who have recently had heart bypass surgery. Bextra is also a cox-2 inhibitor type of drug.
WASHINGTON (Reuters) - Pfizer Inc. has agreed to suspend its advertisements for arthritis drug Celebrex while U.S. regulators review new data that link the drug to an elevated risk of heart attacks, a Food and Drug Administration spokeswoman said on Sunday.
The FDA asked the drug giant on Friday night to temporarily cease the Celebrex ads, and the company agreed, FDA spokeswoman Kathleen Quinn said. Celebrex has been heavily promoted in television commercials and magazine ads, helping propel sales of the drug to nearly $2 billion last year.
The FDA also is working with Pfizer "to develop appropriate information for physicians" about the new findings, Quinn said.
Pfizer could not immediately be reached for comment on Sunday night.
Earlier Sunday, Pfizer Chief Executive Hank McKinnell said doctors should be made aware of the health risks in prescribing Celebrex to their patients, but the company did not plan to recall the popular arthritis drug.
"We're leaving Celebrex on the market because it is an appropriate option for many, many patients," McKinnell said on ABC's "This Week." "Physicians do need to be fully advised of the risks and particularly this new information."
On Friday, Pfizer said Celebrex more than doubled the risk of heart attack in a large cancer-prevention trial, a setback that came just weeks after Merck & Co. recalled its similar Vioxx drug due to heart safety risks.
The FDA on Friday urged doctors to consider prescribing alternatives to Celebrex. The agency said it was leaving all regulatory options open and would have more announcements about Celebrex in the next few days.
Dr. David Graham, associate director for science in the FDA's Office of Drug Safety, criticized the agency for failing to protect the public from dangerous drugs.
"The FDA, I believe, is more concerned with getting drugs on to the market than it is in getting safe drugs on to the market," Graham said on the same television program.
Merck recalled Vioxx on Sept. 30 after a study found that a long-term use of the drug doubled the risk of heart attack and stroke. Both Celebrex and Vioxx belong to a class of drugs known as COX-2 inhibitors. They work by selectively blocking a protein called COX-2 that has been linked to inflammation.
The FDA said on Friday it had serious concerns about the whole range of COX-2 inhibitors, which includes another Pfizer drug called Bextra.
Pfizer said the Celebrex trial, sponsored by the National Cancer Institute, involved patients taking 400-milligram and 800-milligram daily doses of the drug to prevent tumors known as adenomas that grow from glandular tissue. High doses of the anti-inflammatory drug were being tested on the theory that inflammation is a cause of cancer.
Celebrex is one of Pfizer's biggest products, with 2003 sales of $1.9 billion.
Home | Celebrex Information | Celebrex Legal Center | Latest Celebrex News | How to Take Action | Site Map | Disclaimer | Privacy Policy | Securities Litigation Information | Bextra Law Suit Updates | Free Celebrex Law Suit Information | LegalWebMedia | Anapol Schwartz, Celebrex Attorneys | Cohen, Placitella, & Roth, Celebrex Lawyers | Burg Simpson, Celebrex Lawyers | Brent Coon, Celebrex Lawyers | James F. Humphreys, Celebrex Lawyers | Thornton & Naumes, Celebrex Lawyers | Lopez McHugh, Celebrex Lawyers | Breach of Fiduciary Duty Attorneys
© 2006 Celebrex Warning