Rufinamide: CGP 33101, E 2080, RUF 331, Xilep

Abstract

Rufinamide [E 2080, CGP 33101, RUF 331, Inovelon, Xilep] is the lead compound in a series of five-substituted phenylalkyl-3- carbamoyl-4H-1,2,4-triazoles with anticonvulsant activity that was discovered by Novartis AG. Although the precise mechanism of action for rufinamide is unknown, it is known that it limits the firing of sodium-dependent action potentials in neurons, hinting at a membrane-stabilising effect. Rufinamide is under regulatory review in Europe for epilepsy, and phase III trials in the same indication are underway with Eisai in the US. In February 2004, Eisai Co. Ltd announced that it had signed an in-licensing agreement with Novartis Pharma AG for the exclusive worldwide rights to manufacture, develop and market rufinamide for the treatment of epilepsy. Eisai submitted an MAA for rufinamide (Inovelon) as an adjunct therapy of seizures associated with Lennox-Gastaut Syndrome to the European Medicines Agency through the centralised procedure in March 2005. The drug also received orphan drug designation from the European commission in October 2004 for this indication. Eisai also plans to file for regulatory approval in the US. Rufinamide has demonstrated statistically significant efficacy as an adjunctive therapy in adult patients with epilepsy and in patients with seizures associated with Lennox-Gastaut syndrome. Novartis stated in June 2001, prior to the licensing agreement with Eisai, that it had stopped development of rufinamide in the US, Japan and Europe for neuropathic pain (at phase II) and epilepsy (at phase III).