Celgosivir (MX-3253) is a novel antiviral agent being developed as a treatment for chronic hepatitis C by Migenix. Celgosivir and its active metabolite, castanospermine, are potent inhibitors of alpha-glucosidase I, a host enzyme that alters the processing of glycoproteins. Inhibition of this enzyme results in HCV envelope proteins that fail to fold correctly and inhibition of viral assembly and release.

This open-label Phase II dose-ranging trial included 43 patients with genotype 1 HCV who were treatment-naïve or interferon-intolerant. Participants were randomly assigned to one of three celgosivir monotherapy arms:

• 200 mg once daily
• 400 mg once daily
• 200 mg twice daily

Results

Among the 35 patients who completed 12 weeks of therapy, two (5%) had peak HCV viral load reductions of at least 1 log (1.0 log and 2.6 log) during treatment.
Celgosivir was generally well tolerated:

• The most frequently reported side effects were mild-to-moderate gastrointestinal symptoms, with 67% of patients reporting flatulence, 49% diarrhea, and 26% nausea.
  
  
• No serious adverse events were reported.
  
  
• Four patients discontinued therapy due to adverse events.
  
  
• Elevated serum creatine kinase (CK; an enzyme associated with muscle damage) was reported in all treatments groups.
  
  
• CK elevations appeared to be dose related, occurring in 80% of patients in the 400 mg once-daily group, 42% in the 200 mg twice-daily arm, and 19% in the 200 mg once-daily arm.
  
  
• CK elevations were asymptomatic, reversible, and returned to baseline levels within weeks after treatment.

Conclusion

The researchers concluded that celgosivir used as monotherapy was well tolerated in all dosage groups and showed a modest antiviral effect. This study was designed to provide safety and efficacy data needed to proceed to combination therapy trials. Preclinical data suggest that celgosivir may augment the effectiveness of pegylated interferon, with or without ribavirin. 

6/06/06

Reference
E. Yoshida, D. Kunimoto, S.S. Lee, and others. Results of a Phase II dose ranging study of orally administered celgosivir as monotherapy in chronic hepatitis C genotype-1 patients. Abstract S1059. Digestive Disease Week 2006. May 20-25, 2006. Los Angeles, CA.