In this respect, merimepodib has already lost considerable ground to Viramidine, a promising ribavirin prodrug from ICN (NYSE: ICN). Viramidine is much more likely to be a clinically appropriate ribavirin replacement, with a magnitude of benefit likely to obviate a requirement for the co-administration of currently marketed or developmental anti-hepatitis C agents having generated at least preliminary phase II data. Although the current merimepodib data set shows a lack of an increased incidence of ribavirin-associated hemolytic anemia, Viramidine administration has been shown to actually decrease comparative hemolytic anemia rates. Hemolytic anemia is the serious adverse effect that significantly curtails use of ribavirin-based anti-HCV regimens.

The data presented at the HEP DART meeting this week in Hawaii are essentially reiterative, showing that merimepodib met its primary endpoint of safety and tolerability. The drug was not associated with serious adverse events. Merimepodib also met its secondary endpoint of clinical activity. A statistically significant antiviral response and statistically significant dose-dependent antiviral effect was also demonstrated. An ongoing final analysis will include 12-month treatment and six-month post-treatment data.

Merimepodib is a small molecule inhibitor of the enzyme inosine monophosphate dehydrogenase (IMPDH). This action may enhance the antiviral activity of ribavirin, an activity that has been demonstrated in vitro. Whether this strategy can enhance the sustained viral response (SVR) rate in HCV patients, the principal goal of treatment, remains to be seen.

In this investigation, patients were treated with merimepodib 25mg, 50mg, or placebo twice-daily in combination with standard doses of peg-IFN and ribavirin for 24 weeks. Patients achieving undetectable levels of HCV-RNA continued on assigned treatment for an additional 24-week extension phase. Sustained virologic response data are being analyzed. To date, higher-dose merimepodib advantages, over placebo, include:

• a statistically significant, dose-dependent increase in the proportion of recipients achieving undetectable levels of HCV-RNA at 24 weeks (on-treatment analysis)
  • 86% (6 of 7 patients) of 50mg twice daily recipients
  • 33% (2 of 6) of 25mg twice daily recipients
  • 33% (3 of 9) of placebo recipients
• a statistically significant, dose-dependent increase in the proportion of recipients achieving undetectable levels of HCV-RNA on at least one occasion during the study (intent- to-treat population)
  • 73% (8 of 11 patients) of 50mg twice daily recipients
  • 20% (2 of 10) of 25mg twice daily recipients
  • 30% (3 of 10) of placebo recipients.