FDA Panel Backs Safety Claim For Rofecoxib; May Carry Over to Celecoxib

[Guest guest]

FDA Panel Backs Safety Claim For Rofecoxib; May Carry Over to Celecoxib

http://rheumatology.medscape.com/reuters/prof/2001/02/02.12/20010209rglt001.html

WASHINGTON (Reuters Health) Feb 09 - The labeling of Merck's COX-2 inhibitor rofecoxib (Vioxx) should be updated to reflect an apparent safety advantage over the nonsteroidal anti-inflammatory drug naproxen, but the revision should also warn of rofecoxib's comparatively higher cardiovascular risk, an advisory panel to the US Food and Drug Administration concluded on Thursday. The FDA convened a meeting of the Arthritis Advisory Committee to discuss whether data from Merck's large multinational study comparing rofecoxib with naproxen justified a labeling update stating that rofecoxib carries significantly less risk of gastrointestinal effects. Pharmacia failed in a similar bid on Wednesday to convince the committee to support a GI superiority claim for celecoxib over two NSAIDs (see Reuters Health report, February 8). But panel members on Thursday seemed to think that a recommendation to let Merck make the claim should carry over to Pharmacia as well. Pharmacia issued a press release on Thursday afternoon suggesting that it expects that the celecoxib label will be allowed to claim that the drug causes fewer GI effects than ibuprofen and diclofenac, the NSAIDs against which the company tested it. "We look forward to continued interactions and discussions with FDA to determine how the information should be communicated on the Celebrex label," the company said. Panel members agreed that Merck's study demonstrated a safety advantage over NSAIDs regarding GI events such as ulcer, perforation and bleeding. However, the panel stressed that the labeling change should make clear that rofecoxib's superior safety profile was proven only in patients with rheumatoid arthritis and only in those not also taking aspirin. Merck's study also showed a higher rate of cardiovascular events for rofecoxib versus naproxen, and committee members agreed that the elevated risk must be noted in rofecoxib's labeling. The study demonstrated a myocardial infarction rate of 0.5% for rofecoxib and 0.1% for naproxen. There were 22 cardiovascular-related deaths among patients on rofecoxib, compared with 15 deaths in the naproxen group. Rofecoxib's revised labeling should also state that the effect of taking the drug with aspirin is unknown, the panel advised. While the FDA is not required to follow the recommendations of its advisory committees, it almost always does so. Merck's trial, involving about 8,000 patients, compared rofecoxib 50 mg/day — two to four times its recommended dose — with naproxen at normal dosing in rheumatoid arthritis patients. Results of the study, which showed that rofecoxib cut the rate of serious GI events by half and reduced the gravest of these complications by 60% compared with naproxen, were published in Thursday's New England Journal of Medicine. A factor weighing heavily in the panel's decision to support the rofecoxib labeling claim was the fact that the study was able to show a decrease in both symptomatic ulcers and ulcer complications. In contrast, Pharmacia's study of celecoxib versus ibuprofen and diclofenac demonstrated only a decrease in the rate of symptomatic ulcers and ulcer complications combined.