Experimental Nucleoside Inhibitor MK-0608 Suppresses HCV Replication in Chimpanzees

Current therapies for hepatitis C virus (HCV) infection are not always effective and are associated with difficult side effects, spurring research into new antiviral agents.

At the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, taking place this week in San Francisco, researchers from Merck presented animal data on a novel nucleoside inhibitor, MK-0608.

A previous study showed that MK-0608 suppressed HCV replication when administered to HCV-infected chimpanzees for 7 days. In the present study, investigators aimed to determine whether this response would be maintained with longer dosing; infected chimps received MK-0608 once daily for 37 days.

Results

Once-daily oral dosing resulted in a rapid decrease in plasma HCV RNA to below the limit of detection (< 20 IU/ml) in 3 of 4 animals by Day 10.

Continued administration for up to 37 days resulted in sustained suppression of HCV viral load to undetectable levels using the sensitive TMA assay.

Viral load remained undetectable throughout the dosing period.

HCV RNA in the fourth chimpanzee decreased by 4.7 logs during dosing.

In this chimp, selection of resistant virus was not observed.

All animals experienced virological rebound after discontinuation of MK-0608.

Conclusion

"Robust antiviral efficacy was achieved with MK-0608 monotherapy in infected chimpanzees and maintained for over a month's duration without viral breakthrough," the researchers concluded. "While sustained virological response was not obtained with monotherapy for 37 days, the robust and durable antiviral efficacy of MK-0608 makes it a desirable candidate for a co-dosing regimen with other antiviral agents."

09/29/06

Reference
D B Olsen, M Davies, L Handt, and others. The Nucleoside Inhibitor MK-0608 Mediates Suppression of HCV Replication for > 30 days in Chronically Infected Chimpanzees. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA. September 27-30, 2006. Abstract V-1914a.

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