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

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.