CS-8958 (laninamivir prodrug), a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration.

Antimicrobial agents and chemotherapy 2010 Jan 4; In press

Kubo S, Tomozawa T, Kakuta M, Tokumitsu A, Yamashita M

Biological Research Laboratories IV, Daiichi Sankyo Co. Ltd., 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan.

For the treatment and prophylaxis of influenza, two neuraminidase (NA) inhibitors, zanamivir (Relenza(TM)) and oseltamivir phosphate (Tamiflu(TM)), have been licensed. We have reported on laninamivir (code name, R-125489), a novel neuraminidase inhibitor, and have discovered that CS-8958, laninamivir prodrug, worked as a long acting neuraminidase inhibitor in a mouse influenza virus infection model when it was intranasally administered. In this paper, CS-8958 administered just once 7 days before infection showed significant efficacy in vivo. Then, the efficacy by a single administration of CS-8958 after viral infection was compared with that by repeated administrations of oseltamivir phosphate or zanamivir in mice and ferrets and CS-8958 showed superior or similar efficacy to the two licensed NA inhibitors. CS-8958 also significantly reduced the virus titers of an oseltamivir-resistant H1N1 virus with a neuraminidase H274Y substitution in a mouse infection model. These results suggest that, since CS-8958 is characteristically long lasting in the lungs, it may be ideal for the prophylaxis and treatment of influenza.

Keywords: neuraminidase influenza CS-8958 laninamivir