R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus.

Abstract

Roche Holding AG is developing R-1626, an oral nucleoside inhibitor of HCV RNA polymerase. R-1626 has been demonstrated to be well absorbed and rapidly converted to the active component R-1479. The compound has demonstrated a strong capacity to inhibit HCV replication in vitro and in vivo, without the rapid development of viral resistance. After 4 weeks of treatment with R-1626 in combination with PEG-IFN plus ribavirin in treatment-naïve patients with genotype 1 HCV infection, HCV RNA could no longer be detected in approximately 74% of patients, compared with 5% of patients treated with PEG-IFN plus ribavirin alone, indicating the high potency of R-1626 to induce HCV RNA viral load reductions. R-1626 was generally well tolerated, although severe side effects of neutropenia were observed at high doses. A phase IIb clinical trial was ongoing at the time of publication to test the efficacy of R-1626 in combination with a standard or lower dose of PEG-IFN and ribavirin in HCV genotype 1-infected patients. Given its potent antiviral effect with an apparent high genetic barrier, R-1626 represents an important advancement in improving the outcome of patients with chronic HCV infection.

• Authors: Pierluigi Toniutto, Carlo Fabris, Davide Bitetto, Elisa Fumolo, Ezio Fornasiere, Mario Pirisi
• Journal: IDrugs : the investigational drugs journal (IDrugs) Vol. 11 Issue 10 Pg. 738-49 (Oct 2008) ISSN: 1369-7056 [Print] England
• PMID: 18828074 (Publication Type: Journal Article, Review)

Chemical References

• Antiviral Agents
• Enzyme Inhibitors
• Nucleosides
• Prodrugs
• RNA, Viral
• Viral Nonstructural Proteins
• NS-5 protein, hepatitis C virus
• balapiravir

Topics

• Administration, Oral
• Animals
• Antiviral Agents (administration & dosage, therapeutic use)
• Drug Evaluation, Preclinical
• Drug Resistance, Viral
• Drug Therapy, Combination
• Enzyme Inhibitors (administration & dosage, therapeutic use)
• Hepacivirus (drug effects, enzymology, genetics)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Molecular Structure
• Nucleosides (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Patents as Topic
• Prodrugs (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• RNA, Viral (blood)
• Structure-Activity Relationship
• Treatment Outcome
• Viral Load
• Viral Nonstructural Proteins (adverse effects, antagonists & inhibitors, metabolism, pharmacokinetics)