Novartis withdraws COX-2 inhibitor lumiracoxib from Canadian market over concerns of serious liver adverse events

The decision by Health Canada to revoke marketing authorization follows a recent "not approvable" decision by the U.S. Food and Drug Administration.

Complying with a request from Health Canada, Novartis Pharmaceuticals Canada has ceased sales and marketing of its selective COX-2 inhibitor Prexige, the company announced in a press release.

Novartis has marketed Prexige (lumiracoxib) in Canada since November 2006 for treating the signs and symptoms of knee osteoarthritis (OA) in adults, with a maximum daily dose of 100 mg.

In July, Canadian authorities expanded the approved indications to include treating OA in all joints. That decision was based on a review of a clinical trial database for lumiracoxib, which comprised about 40,000 patients, according to a Novartis press release.

But after reviewing additional safety information submitted by Novartis, Health Canada decided to withdraw the drug's market authorization.

The agency had requested the information from Novartis after lumiracoxib was removed from the Australian market in August, which followed reports of serious liver adverse events linked to the drug at daily doses of 200 mg and 400 mg, according to a press release from Health Canada.

As a result of its review, Health Canada concluded that the risk of serious liver-related adverse events with lumiracoxib cannot be safely and effectively managed at the 100 mg daily dose, the release said.

The decision by Health Canada also follows a recent decision by the U.S. Food and Drug Administration that the drug is "not approvable" as a once-daily treatment for OA pain.

The FDA noted in its response that it remained open to exploring the use of the drug in patients where lumiracoxib would provide an acceptable benefit-to-risk balance, which could include patients with a higher incidence of gastrointestinal complications.

The clinical data provided by Novartis to both the FDA and Health Canada regarding lumiracoxib's liver safety profile, for the 100 mg daily dose, included studies with up to 12 months follow-up. The data showed that 0.85% of patients had elevations of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) similar to levels seen with currently available NSAIDs. There were also no cases of either jaundice or hepatic failure, according to the Novartis press release.

The submission also included data from the TARGET study, which involved over 18,000 patients. The results of this study showed that lumiracoxib reduced the incidence of serious upper gastrointestinal complications by 79% compared to two other common NSAIDs in patients who were not taking aspirin. Also, the drug was associated with significantly lower blood pressure increases compared to Aleve [naproxen, Bayer HealthCare] and ibuprofen, with no significant difference in cardiovascular events such as heart attack or stroke, according to the release.