ABSTRACT
Clevudine (l-FMAU) is the unnatural l-enantiomer of the natural nucleoside d-thymidine and has potent antiviral activity against hepadnaviruses including hepatitis B virus (HBV) in vitro and in vivo. Its mode of action is by inhibition of the viral polymerase. Clevudine was discovered at Yale University (Chu et al., 1995) and licensed to Bukwang, a Korean pharmaceutical company, and also to Pharmasset for further development and marketing. Clevudine is now approved by the Korean Food and Drug Administration (FDA) for the treatment of adults with chronic hepatitis B virus infection (CHB), but it is not yet approved by other regulatory agencies. It is available only as tablets for oral administration. The drug is currently undergoing several randomized, double-blind, active control clinical trials in patients with CHB to evaluate its efficacy compared with both lamivudine and adefovir (clinical trials NCT00362635, NCT00496158, and NCT00496002); the outcome of these trials suggests strongly that clevudine is less effective and more toxic than entecavir and tenofovir; for efficacy it is approximately equivalent to lamivudine but it is also more toxic than that drug.
