The Food and Drug Administration should immediately yank Celebrex and Bextra from the market to protect Americans from the drugs’ heart risks, according to a petition filed with the agency yesterday by Public Citizen. The petition also requests that the FDA freeze applications for Arcoxia and Prexige, two painkillers under development for the same reason.
Meanwhile, months after Vioxx was removed from the market for causing heart woes, The Lancet today published an agency whistle-blower’s study indicating that the painkiller caused up to 140,000 extra cases of serious coronary heart disease. It’s a fiasco for which the FDA is culpable and one that merits a congressional response, says the study’s lead author Dr. David J. Graham.
In 14 studies reviewed by Public Citizen, a nonprofit consumer advocacy organization, the newer-generation painkillers were shown to be neither more effective nor safer on the stomach than older, cheaper counterparts like ibuprofen, and “there is mounting evidence of cardiac toxicity with these drugs similar to that seen with Vioxx,” the 19-page petition states.
Dr. Sidney Wolfe, health research group director at Public Citizen, said more than 36 million prescriptions were written for Bextra and Celebrex in 2004, which justifies not waiting for the February FDA meeting.
“Every month that goes by is another several million people who get prescriptions for these drugs,” Wolfe said. “Given the quite clear evidence of increased cardiovascular risk, I just don’t feel comfortable waiting.”
The FDA did not immediately respond to a request for comment.
From Feb. 16 to 18 the FDA will gather federal advisers to discuss the benefits and risks of cox-2 inhibitors, new-generation painkillers that block an enzyme linked to inflammation. That meeting coincides with a similar panel to be held in mid-February by European health officials.
Pfizer Inc., maker of Celebrex and Bextra, issued a statement saying the company “remains confident in its cox-2 medicines as important treatment options that provide necessary pain relief for patients around the world.”
Prodded by the FDA, Pfizer silenced its advertising for both painkillers. The firm also added a link on its site to the FDA’s statement about a colon polyp prevention trial studying Celebrex that was halted because the painkiller was linked to up to 3.4 times greater risk of cardiovascular events.
Pfizer’s statement said the company looked forward to the FDA committee conducting “a scientific and reasoned evaluation.”
Merck & Co. has received a letter from the FDA saying the agency could approve Arcoxia, with additional studies. Anita Larsen, a Merck spokeswoman, said it is “inappropriate to comment” on the petition before the FDA meeting.
Novartis, manufacturer of Prexige, did not return calls for comment.
The Lancet planned to publish Graham’s paper in November, on the eve of a high-profile congressional hearing on Vioxx, but the FDA held up publication by refusing to approve the paper. Without the agency’s approval, Graham, an FDA employee, withdrew the paper fearing he might be fired.
The FDA first objected after reviewing a summary of the report’s findings that high doses of Vioxx left people 3.6 times more likely to suffer coronary heart disease, compared with Celebrex. Vioxx remained on the market and a supervisor suggested warning its manufacturer, Merck, “so they can be prepared for extensive media attention,” according to internal e-mails released by US Senator Chuck Grassley, an Iowa Republican.
“It seems to me that the people with the vested interest in the status quo, those who sought to block the publication of this article and who sought to keep this information from the public, the ones who are, in many ways, responsible for this excess of heart attack, injury, and death with Vioxx,” said Graham, associate director for science and medicine in the FDA’s Office of Drug Safety.
In a statement, the agency said Dr. Steven Galson, acting director for FDA’s Center for Drug Evaluation and Research, contacted the journal because Graham ignored standard internal peer review.
“While many scientists at FDA may not fully agree with some of the conclusions in Dr. Graham’s paper, having Dr. Graham’s paper published in a peer-reviewed journal will contribute to the agency’s ongoing discussions about the safety of the entire class of nonsteroidal anti-inflammatory drugs, which will include a public advisory committee meeting in February,” the FDA said.
Merck discounted Graham’s numbers. “An estimate of harm from Vioxx is speculation,” said Larsen, who noted that genetics, smoking, and other risk factors can cause heart problems. “Determination of whether Vioxx was responsible for any patient’s myocardial infarction or stroke can only be made on a case-by-case basis.”
The Vioxx debacle should prompt Congress to create a separate office of drug safety, Graham said. Absent that, officials who approve drugs can unduly influence whether those drugs are removed from the market.
Proposals floated this session would create a separate office of drug safety to better protect Americans when prescription drugs are used by millions. The first of many measures was announced last week by US Senator Christopher Dodd, a Connecticut Democrat. The proposal would create an Office of Patient Protection and would give that office power to yank an unsafe drug from the market, halt ads for unsafe drugs, and impose restrictions on use.