Global Insight Perspective | |
Significance | Australia's Therapeutic Goods Administration (TGA) has banned the sale of Novartis's (Switzerland) COX-2 inhibitor Prexige (lumiracoxib), in the light of eight reports of serious adverse liver reactions to the drug, including two deaths and two liver transplants. |
Implications | Prexige has been marketed by Novartis in Australia since 2005, and was listed on the Pharmaceutical Benefits Scheme (PBS) in 2006. At the time of its listing, concerns had been raised over the product's safety profile. However, in common with other COX-2s, these had been in connection with possible risks to the heart. |
Outlook | Despite the ban, Novartis maintains that Prexige has a positive benefit-to-risk profile. In light of this, the company has pledged to continue to roll out the drug on a global level. However, the company's chances of gaining marketing authorisation in a number of major markets, notably the United States, will inevitably be seriously reduced. |
The Therapeutic Goods Administration (TGA)'s decision to ban Prexige came in response to a recommendation from the organisation's Adverse Drug Reactions Advisory Committee (ADRAC), which had been investigating eight reports of serious adverse liver reactions to the drug, including two deaths and two liver transplants. According to the TGA's Principal Medical Adviser Dr Rohan Hammett, "The TGA has taken this advice…in order to prevent further cases of severe liver damage. It seems that the longer people are on the medicine, the greater the chance of liver injury." Hammett also commented: "There may well be many other patients out there who have a degree of liver damage that hopefully will get better when they stop the drug."
Novartis Australia has been quick to comply with the TGA's request, and has urged all patients who are taking Prexige to stop taking the treatment immediately. Patients have also been urged to return any remaining Prexige tablets to their pharmacist, who will give them a full refund. Novartis estimates that approximately 60,000 patients have used Prexige in Australia, with the majority of these being prescribed Prexige 200 mg for the management of osteoarthritis. Other indications include relief of acute pain, including post-operative pain, and pain related to dental procedures and relief of pain due to primary dysmenorrhoea.
Global Roll-Out Continues
Despite Novartis's speedy compliance, the company has stated that it continues to believe that the drug has a positive benefit-to-risk profile. In addition, it has pointed out that liver failure is a rare, but recognised, side-effect for all COX-2 inhibitors, as well as for other types of non-steroidal anti-inflammatory drugs (NSAIDs). In light of this, Novartis has confirmed that it will continue its policy of rolling out the drug around the world, although the company has pledged to inform relevant country health authorities about the Australian withdrawal.
As things stand, Prexige has been approved in over 50 countries. It is currently in the process of being rolled out in Europe, while the company is also planning to seek marketing authorisation in the United States. More than 7 million prescriptions have been issued worldwide since it was first launched in 2005, although the product's worldwide sales in the first half of 2007 were a fairly modest US$52 million.
Outlook and Implications
According to Novartis, Prexige was first made available to patients in Australia in November 2005, and the drug began being widely used after it was listed on the Pharmaceutical Benefits Scheme (PBS) in 2006. Although safety concerns were voiced at the time, these concerns centred on the drug's potential long-term heart, rather than liver, risks (see Australia: 2 August 2006: COX-2 Inhibitor Prexige Listed on PBS, but Doctors Warn of Heart Risk).
C0X-2 Inhibitors as a class have of course been under close scrutiny since 2004, when Merck's (U.S.) Vioxx (rofecoxib) was withdrawn from markets around the world, after being linked to an increased risk of heart attack. In this context, Prexige was already facing an uphill battle to gain marketing authorisation in the United States, even without its association with serious adverse liver reactions. The ban on Prexige in Australia will inevitably make it that much more difficult for Novartis to introduce the drug in the United States, while the further roll-out in Europe, and its continued availability in its existing markets, must also be called into question.
Prior to the fallout from Vioxx, Prexige had been considered to be a potential global blockbuster. However, the Australian ban, which is the first in the world, represents another major setback for Prexige. It also piles additional pressure onto Novartis, which has recently revised downwards its full-year forecast for 2007, partly on account of a suspension in U.S. sales of its bowel disorder treatment Zelnorm, after it was linked with serious cardiac side-effects (see Switzerland: 17 July 2007: Novartis Lowers FY Outlook as Usual Bestsellers Offset Pharmaceutical Division Setbacks).