Laninamivir and its prodrug, CS-8958: long-acting neuraminidase inhibitors for the treatment of influenza.
Oseltamivir and zanamivir are currently licensed worldwide for influenza treatment and chemoprophylaxis. Both drugs require twice-daily administration for 5 days for treatment. A new influenza drug, laninamivir (code name R-125489), and its prodrug form, CS-8958 (laninamivir octanoate or laninamivir prodrug), which are long-acting neuraminidase inhibitors, are introduced in this review. Laninamivir potently inhibited the neuraminidase activities of various influenza A and B viruses, including subtypes N1-N9, pandemic (2009) H1N1 virus, highly pathogenic avian influenza (HPAI) H5N1 viruses and oseltamivir-resistant viruses. Because of the long retention of laninamivir in mouse lungs after an intranasal administration of CS-8958, therapeutic administration of a single dose of CS-8958 showed superior efficacy to repeated administrations of zanamivir or oseltamivir in animal infection models for influenza A and B viruses. These include pandemic (2009) H1N1 virus and HPAI H5N1 virus. Prophylactic single administration of CS-8958, as early as 7 days prior to infection, also showed superior efficacy. Finally, the potential of a single inhalation of CS-8958 for influenza patients was demonstrated by clinical studies, and CS-8958 has been approved and is commercially available as Inavir(®) (Daiichi Sankyo Co., Ltd, Tokyo) in Japan.
Biological Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan. yamashita.makoto.yr@daiichisankyo.co.jp
Makoto
M
Yamashita
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D006146:Guanidines; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009975:Orthomyxoviridae / Q000472:pathogenicity / Q000502:physiology; D053139:Oseltamivir / Q000494:pharmacology*; D058873:Pandemics; D011355:Prodrugs / Q000494:pharmacology*; D011714:Pyrans; D051381:Rats; D012794:Sialic Acids; D053243:Zanamivir / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; C546919:CS 8958; D006146:Guanidines; D011355:Prodrugs; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; C546918:laninamivir; D009439:Neuraminidase; D053243:Zanamivir