Antimicrob Agents Chemother. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.

[Giuseppe]

Antimicrob Agents Chemother. 2008 Oct 27. [Epub ahead of print]

CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.

Yamashita M, Tomozawa T, Kakuta M, Tokumitsu A, Nasu H, Kubo S. - 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.

In this paper, the new potent NA inhibitor R-125489 is reported for the first time.

R-125489 inhibited the NA activities of various type A and B influenza viruses including N1-N9 subtypes and Tamiflu resistant viruses.

The survival effect of R-125489 was shown to be similar to that of zanamivir by an intranasal administration route in a mouse/influenza virus A/PR/8/34 infection model.

Moreover, we found that the esterified form of R-125489 showed improved efficacy compared to R-125489 and zanamivir, depending on the acyl chain length, and that 3-(O)-octanoyl R-125489 (CS-8958) was the best compound (p<0.0001, compared to zanamivir) in the same infection model.

A prolonged survival effect was observed after a single administration of CS-8958 even seven days before infection.

It is suggested that intranasally administered CS-8958 works as a long-acting NA inhibitor (LANI) and shows in vivo efficacy as a result of a single intranasal administration.

PMID: 18955520 [PubMed - as supplied by publisher
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[Shiloh]

Re: Antimicrob Agents Chemother. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.

Source: http://www.biotechnews.com.au/article/267604/asian_flu_study_marvel

Asian flu study a MARVEL
Biota?s next-generation flu treatment moves into Phase III
Kate McDonald (Australian Life Scientist) 17/11/2008 13:15:00

Phase III trials of Biota?s neuraminidase inhibitor CS-8958 for influenza are set to begin in several centres throughout Asia.

CS-8958, which was discovered by Japanese pharma Daiichi Sankyo and is co-owned by Biota, is a long-acting neuraminidase inhibitor (LANI) that early trials suggest is effective against influenza A and B as well as the H5N1 bird flu virus.

It is hoped that a single inhaled dose will be efficacious for treatment of flu and another once a week for prophylaxis.

The Phase III trial, nicknamed MARVEL, will be conducted in multiple centres in Japan, Taiwan, Hong Kong and Korea, in time for the Asian flu season. As well as the Phase III trial in adults, a Phase II/III study will be conducted in Japan for paediatric indications.

The duration of the trial will depend on the availability of patients and the extent of the flu season, Biota said in a statement.