Pfizer’s one-time blockbuster painkiller Celebrex (celecoxib) is an effective treatment for preventing colorectal polyps, a precancerous condition, but the looming spectre of its effect on the heart has raised its ugly head again and the researchers say the potential for cardiovascular events outweigh the benefits in this patient population and should not be used routinely in this indication.
In two studies in yesterday’s New England Journal of Medicine enrolling more than 3,500 patients, investigators set out to determine whether inhibition of the COX-2 receptor using Celebrex prevented the re-appearance of polyps in patients who had previously had growths removed, and followed up with colonoscopies at year one and year three. Results were significantly in favour of Celebrex, with just 34%-43% of patients given the active therapy going on to develop polyps over the study period versus 49%-60% of those in the placebo group.
But there was a big jump in the risk of serious cardiovascular problems, with 2.5% of subjects in the Celebrex group experiencing a heart attack, stroke or heart failure versus 1.9% of those given dummy pills. Researchers say the drug should not be routinely used to prevent colon cancer: "The cardiovascular risks far outweigh even the most optimistic estimates of the potential benefit on colorectal cancer," commented Bruce Psaty, who wrote an accompanying editorial for the studies, reported by Bloomberg.
Merck & Co pulled its COX-2 offering Vioxx (rofecoxib) from the global marketplace in 2004 after a similar study showed a doubling in the risk of heart attack and stroke in patients given the drug for 18 months or longer. And Pfizer has struggled to keep its once $3 billion drug going, particularly after dosing in two trials of Celebrex was stopped later that year because of a raised cardiovascular event risk. Then it was given a black box warning by the US Food and Drug Administration and saw sales in the fourth quarter of 2005 halved. But it has been making gains again, with revenues boosted 17% in the second quarter of this year to $471 million – and is still a big selling drug for the firm.
The dose used in colorectal trials is greater than that used in arthritis patients, so the impact on this patient group is unknown. Pfizer is gambling on a 20,000-patient study that it hopes will prove once and for all that Celebrex is effective and no more likely to cause cardiovascular side effects than the older non-steroidal anti-inflammatory drugs ibuprofen and naproxen.