FDA has issued a "not approvable" letter for Arcoxia (etoricoxib) for the treatment of osteoarthritis symptoms, Merck announced April 27.

"FDA indicated that Merck would need to provide additional data in support of the benefit-to-risk profile for the proposed doses of Arcoxia in order to gain approval," the firm stated. The company declined to comment on whether it intends to submit that additional data, or if further studies would be required.

The agency's decision is not surprising, given the recommendation of its Arthritis Drugs Advisory Committee, which voted 20-1 against approval during an April 12 panel meeting (¹ Also see "Arcoxia GI Benefit Does Not Outweigh CV Risk, Committee Says" - Pink Sheet, 12 April, 2007.).

The committee concluded that the increased risk of serious cardiovascular adverse events seen in pivotal trials outweighed the COX-2 inhibitor's favorable impact on gastrointestinal tolerability. In particular, panel members said further study of the safety profile of 30 mg proposed starting dose was needed.

Prior to the committee meeting, Merck seemed reasonably confident Arcoxia stood a chance at approval. The firm even included U.S. etoricoxib sales in its 2007 earnings guidance.

The Vioxx follow-on was deemed "approvable" by FDA in 2004. Merck resubmitted its NDA in November with data from the nearly 35,000-patient MEDAL trial, which compared etoricoxib with the non-steroidal anti-inflammatory drug diclofenac (² Also see "Merck Seeks Narrowed Arcoxia Indication In Response To “Approvable” Letter" - Pink Sheet, 10 November, 2006.).

Whether the fate of Arcoxia will also befall Novartis' COX-2 inhibitor Prexige (lumiracoxib) is unclear. During the company's April 23 first-quarter earnings call, Novartis Global Pharma Development Head James Shannon said that although there is no FDA advisory committee review on the schedule yet, "it would not surprise me if we had a panel for Prexige."

FDA issued a "not approvable" letter for lumiracoxib in 2003, primarily because of liver toxicity concerns. The firm plans to resubmit the drug for osteoarthritis, based on results of its 18,000-patient TARGET trial, in the first half of 2007. Shannon maintained that Prexige does not raise the same safety issues cited by the Arcoxia panel.

- Brooke McManus (b.mcmanus@elsevier.com)

FDA Cold-Cox Merck; Arcoxia “Not Approvable” For Osteoarthritis

More from Archive

More from Pink Sheet