Novartis’ problems with its COX-2 inhibitor Prexige took a turn for the worse yesterday, when regulators in the UK and Germany suspended marketing licenses on safety concerns about the drug, following in the footsteps of Australia, Turkey and Canada.

The Medicines and Healthcare products Regulatory Agency says it has informed health professionals in the UK to stop prescribing Prexige (lumiracoxib) for osteoarthritic pain on fears of possible liver damage, following a review by the Commission on Human Medicines which showed an increase in serious liver reactions occurring with the licensed 100mg dose which, in some cases, developed in under a month.

The move follows a tightening of prescribing restrictions in the UK in August to protect patients with liver problems, as well as additional requirements for blood tests before and during Prexige treatment for all others. But, “in light of the latest data on liver toxicity associated with lumiracoxib, the Commission on Human Medicines advised that previous measures could not be relied upon to guarantee patient safety”, said Dr June Raine, Director of Vigilance and Risk Management of Medicines at the MHRA, explaining the decision.

A spokeswoman for the MHRA told PharmaTimes UK News that marketing authorisation has been suspended pending the results of a European-wide review, the results of which will determine whether the drug is withdrawn totally or put back on pharmacy shelves. The review is being undertaken by the European Medicines Agency’s Committee for Medicinal Products for Human Use, which is due to meet in December to discuss the issue, she said.

US rejection
Prexige was first launched in Brazil in 2005 but, in August this year, Australian health regulators withdrew the drug from the market following reports of serious liver adverse events that were linked to the drug at doses of 200mg and 400mg daily. This was followed by a “not approvable” letter from the US Food and Drug Administration at the end of September, and Health Canada’s move to pull the drug from pharmacy shelves in October.

From its launch until October 26, 2007, there have been 159 spontaneous reports of suspected adverse liver reactions to Prexige, of which 91 were considered serious and 68 non-serious, while two had a fatal outcome. From March 2006 to November 13, 2007, there were 23 reports of suspected adverse reactions in the UK, the MHRA said.

But Novartis remains steadfast in its belief in the product. In an e-mailed statement, a company spokesperson told PharmaTimes UK News: “Novartis continues to believe Prexige is an important treatment option with a positive benefit/risk ratio when used in appropriate patients, especially those at high risk of gastrointestinal complications…Novartis will continue discussions with European health regulators”.

Investors in the company seemed to take the news in their stride; after a day’s heavy trading shares closed down just 1.3% at $52.13 on the New York Stock Exchange.