Global Insight Perspective | |
Significance | Prexige was withdrawn from the British, German and Austrian markets yesterday, and its benefit/risk profile is being re-examined by the European central health regulator. |
Implications | The possibility for European withdrawal follows Prexige's ban from the Canadian and Australian markets as well as a marketing application rejection from the U.S. FDA. |
Outlook | As Prexige's marketing approval comes under scrutiny in Europe, Novartis sees its hope of the painkiller achieving blockbuster status fade even further. This could also prompt a safety re-evaluation where Prexige is still marketed. |
Swiss giant Novartis has announced that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and Federal German Regulator BfArM have ordered the market withdrawal of its COX-2 inhibitor anti-inflammatory pain killer Prexige over liver toxicity concerns. Pending a decision from the Committee for Medicinal Products for Human Use (CHMP), which is part of the European Medicines Agency (EMEA), Prexige will also be withdrawn from the Austrian market. The market suspensions follow last week's CHMP decision to re-evaluate Prexige's benefit/risk profile under article 107, and more European countries could decide to suspend marketing of the drug in anticipation of the CHMP's review expected in December.
Once-daily 100 mg Prexige gained marketing approval for the treatment of osteoarthritis-associated pain in all 26 European Union (EU) member-states barely a year ago (see Switzerland: 07 November 2006: Novartis Gets EU Approval for COX-2 Inhibitor Prexige), after successfully completing the Mutual Recognition Procedure, with the United Kingdom acting as the reference member-state. Last August, Novartis informed European doctors that Prexige should not be prescribed for patients with or at risk of liver diseases (see Switzerland: 28 August 2007: Novartis Warns European Doctors Over New Prexige Restrictions). The possibility of a sales ban in Europe follows full market withdrawals in Canada and Australia (see Canada - Switzerland: 05 October 2007: Health Canada Orders Market Withdrawal of Prexige and Australia: 13 August 2007: Liver Worries Prompt Australia's TGA to Ban Novartis's Prexige)and partial market withdrawal in New Zealand (see New Zealand: 21 August 2007: Medsafe Bans High-Dosage Prexige in New Zealand). Health Canada's decision was based on reports of four adverse hepatic reactions involving Prexige 100 mg, whereas the Australian Therapeutic Goods Administration's decision came after reports of eight adverse hepatic events in patients taking higher dosages of Prexige, including two deaths and two people requiring liver transplants. Novartis has declared that the incidence of liver damage in patients taking Prexige 100 mg was not outside the norm for this type of drug.
Cox-2 inhibitors specifically inhibit Cox-2, an enzyme responsible for inflammation and pain. Cox-2 inhibitors rapidly became popular pain killers, achieving blockbuster status due to their decreased risks of gastrointestinal bleeding, but very soon found themselves in the spotlight for severe side effects. Hence, due to cardiovascular risks, Merck & Co.'s (U.S.) Vioxx (rofecoxib) and Pfizer's (U.S.) Bextra (valdecoxib) were withdrawn from the global market in 2004 and 2005, respectively.
Outlook and implications
Prexige follows in the steps of other Cox-2 inhibitors by raising serious safety concerns. Although the CHMP has yet to give revised recommendations over the drug's benefit/risk profile, Prexige's sales have now been suspended in three European markets, with possibly more to follow. With the prospect of the painkiller being banned for sales in Europe as early as next month and following the FDA's rejection for approval in the world's largest pharmaceutical market (see Switzerland: 27 September 2007: Novartis Receives Non-Approvable Letter for Cox-2 Prexige), Novartis is witnessing Prexige's potential blockbuster status fade even further. In Europe, sales of Prexige generated US$8 million in revenues for the first nine months of 2007.
Worryingly for the Swiss pharma company, Prexige was approved in Europe at the low 100 mg dosage, and, should the CHMP advise against commercialisation, this could prompt other regulators to re-evaluate the painkiller's safety profile. Initially, Prexige was approved in more than 50 markets. Regardless of the outcome, this is another sign that Cox-2 inhibitors are still under intense scrutiny for harmful effects and U.S. Pfizer's Celebrex (celecoxib) could be next on the list, even if for now it hurries to claim the market share of its disgraced competitors.
This development comes shortly after the announcement of liver safety concerns over Novartis's type 2 diabetes drug Galvus (see Switzerland: 06 November 2007: Safety Concerns for High-Dose Galvus See Novartis Delay European Launch). Although Prexige is not one of Norvartis's top-twenty sellers, the company's revenues are expected to suffer and it could see its unexciting full-year revenue projection take another dip (see Switzerland: 17 July 2007: Novartis Lowers FY Outlook as Usual Bestsellers Offset Pharmaceutical Division Setbacks).