FDA panel document notes concerns on Exanta safety and efficacy

Although the US Food and Drug Administration advisory panel reviewingAstraZeneca's Exanta (ximelagatran) had yet to meet (the hearing is scheduled for 13.30 UK time on September 10), the company's share priced moved lower on September 9, as panel documents on the drug were released indicating concerns on the safety and efficacy of the drug.

In terms of efficacy, the Exanta SPORTIF trials were powered to show non-inferiority to warfarin. The FDA documents noted that the 2% margin chosen to measure non-inferiority was too liberal, and said that a margin of this magnitude could leave open the possibility that Exanta was only half as effective as warfarin and still be considered non-inferior to warfarin.

On safety, the FDA document says that liver enzyme monitoring on the label (as proposed by AstraZeneca) may not be adequate to control safety, as the intense monitoring in the Phase II studies failed to prevent two deaths owing to liver failure. It also noted that the company's proposed label has no provisions for dose adjustment in patients with varying degrees of renal impairment and that this may compromise safety. It is highlighted that blood levels of Exanta are five times higher in renally -impaired patients.