The
Food and Drug Administration intervention on Thursday, against Pfizer's Bextra
and Celebrex ends any remaining notion that Cox-2 pain inhibitors are wonder
drugs.Pfizer forced to swallow bitter pill
The
Food and Drug Administration intervention on Thursday, against Pfizer's Bextra
and Celebrex ends any remaining notion that Cox-2 pain inhibitors are wonder
drugs.
Pfizer's withdrawal of Bextra, at the FDA's request, leaves only one of three blockbusters in the Cox-2 class on the US market - a considerable retreat since the controversy over safety erupted in September and Merck withdrew Vioxx.
Even Celebrex, the lone survivor, must now carry the strongest warning possible in its labelling, alerting users to its potential to increase the risk of heart attack and strokes.
The FDA's mandated “black box” warning will also apply to other prescription anti-inflammatory pain drugs, including Boehringer Ingelheim's Mobic.
The moves reflect a collapse in confidence in Cox-2 drugs following the Vioxx withdrawal that has been both sudden and unexpected.
The labelling requirement is a double blow to the industry: not only does it put Cox-2s on equal footing with older, cheaper medications but it could also raise the hurdle substantially for the approval of other experimental Cox-2 drugs, such as Merck's Arcoxia, Novartis's Prexige, and a compound by GlaxoSmithKline.
Cox-2 inhibitors were launched in 1999 as super-aspirin painkillers. Heavily marketed, the products quickly hit sales of $1bn a year, on the back of a promise that they were safer than existing chronic pain medicines because they reduced the risk of stomach ulcers.
Critics said they were over-prescribed, overpriced and alleviated pain no better than cheaper, over-the-counter products, such as ibuprofen.
The FDA said only Vioxx had proven abilities to ease stomach bleeding in at-risk patients. Thursday's decision yesterday recasts Celebrex as another pain medicine in the category of non-steroidal anti-inflammatory drugs, or Nsaids.
The black-box warning on all prescription Nsaids will advise of the “potential for increased risk of cardiovascular events and the well-described, serious, and potentially life-threatening gastrointestinal bleeding associated with these drugs”.
The FDA also recommended that Celebrex be used at the lowest effective dose, for the shortest duration. It asked for a long-term safety study on Celebrex.
Pfizer sees the FDA's decision as a chance to show that other, older pain drugs are untested and pose relative heart risks of their own.
It takes solace from the fact that prescriptions drugs such as Mobic and diclofenac must also carry the black box heart risk warning and that the FDA said they should not be used for heart surgery patients.
“The FDA is acknowledging that there is inherent risks in those older Nsaids,” Pfizer said.
Drugmakers also saw a positive side to the FDA's request for new labelling about the safe use of ibuprofen and naproxen.
Thursday's tough line appears to be intended to quell concerns that the FDA had been lax in its earlier monitored safety of Cox-2 and other drugs.
In February, an expert panel said all three drugs - Vioxx, Bextra and Celebrex - were safe enough to be marketed. Merck had already indicated it would consider bringing Vioxx back, if allowed. Thursday's action seems to dash those immediate hopes. The industry has been taken by surprise, but February's expert panel vote on Bextra and Vioxx had been close. The FDA said it believed the entire class caused heart risks and disregarded the expert advice on Bextra because the drugs few demonstrable benefits did not outwight its risks.