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Clevudine 48 Weeks
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Reported by Jules Levin
EASL, April 2006, Vienna, Austria
"A 48-week clevudine therapy demonstrated significant viral suppression and biochemical improvement in naïve patients with chronic hepatitis B"
Young-Hwa Chung 1, KS Lee 2, JH Kim3, SH Ryu4, SW Paik 5, SH Um6, BH Han7, M Cho8, KS Byun 6, BI Kim5, JW Park9, HJ Lee10, JY Han 11, HC Kim12, SG Hwang13, K Yoo 14, YS Lee11, YJ Lee4, YS Kim15, JM Yang11, CY Chon2, SH Cho11, YS Kim16, SK Choi17, YO Kweon18, CJ Han19, JS Hwang20, MS Lee21, DG Kim22, HY Lee23, JY Choi11, HW Yoo24, MJ Otto25, PA Furman25, HS Lee26, BC Yoo 5
1AMC 2YUH 3GMS 4IUH 5SMC 6KUH 7KMS 8PNUH 9NCC 10YUMC 11CUK 12WUH 13PCUH 14EWUH 15IUH 16SCUH 17CNUH 18KNUH 19KIRMS 20KUDMC 21HUH 22CNUH 23CUH 24Bukwang Pharm. Co., Ltd. 25Pharmasset Inc. 26SNUH
Clevudine (L-FMAU)
- Pyrimidine nucleoside analogue
(L- enantiomer)
- Potent inhibition of HBV replication
Inhibition of synthesis of dsDNA from ssDNA
Suppression of cccDNA
- No cytotoxicity or mitochondrial toxicity
- Rapid absorption, long half life
- Major route of elimination: renal excretion
L-FMAU, 1-(2-deoxy-2-fluoro-_-L-arabinofuranosyl)thymine
Clevudine showed potent and durable antiviral activities during
a 12-week clevudine therapy in HBeAg-positive CH-B.
Clevudine characteristically induced sustained post-treatment
antiviral effects after the 12-week treatment period.
Baseline Characteristics of Naïve HBeAg+ CHB Patients
Treated with Clevudine for 48 weeks (N=40)
N=9 HBV DNA >4,700 copies/mL
Normal serum ALT
N=30 HBV DNA >4,700 copies/mL
High serum ALT
N=1 HBV DNA <4,700 copies/mL
Normal serum ALT
Baseline Characteristics of Naïve HBeAg- CHB Patients
Treated with Clevudine for 48 weeks (N=15)
N=5 HBV DNA >4,700 copies/mL
Normal serum ALT
N=10 HBV DNA >4,700 copies/mL
High serum ALT
Inclusion and Exclusion Criteria
of 24-week Clevudine Therapy
Inclusion Criteria
- HBV DNA levels >106 copies/mL (1 million)
- Serum ALT level: 2 to 10 times of ULN
Exclusion Criteria
- HIV or HCV seropositivity
- Hepatocellular carcinoma or decompensated LC
- Other significant associated diseases in other organs
- Breastfeeding and pregnant women
- Previous treatment with any nucleoside analogue
Methods
1. Measurement of serum HBV-DNA
Digene Ultra-sensitive Hybrid Capture II HBV DNA test
-- From baseline to the end of the study.
-- Lower LOD of 4,700 copies/mL
COBAS Amplicor HBV monitor test
-- When HBV DNA levels reduced to <4,700 copies/mL
-- Lower LOD of 300 copies/mL
2. Determination of HBeAg and Anti-HBe
- Radioimmunoassay (Abbott Laboratories, North Chicago, IL)
3. Serum ALT level
Author Summary
A 48-week clevudine therapy demonstrated significant viral suppression and biochemical improvement in naïve patients with chronic hepatitis B.
-- Clevudine showed sustained antiviral effect after the cessation of therapy
-- All the patients who achieved negative HBV-DNA by PCR at the week 24 showed sustained viral and biochemical responses during the maintenance therapy with lower dose.
-- No serious adverse event was observed during the 48-week clevudine therapy.
Conclusion
Clevudine may have promising potentials as a safe and effective antiviral
agent for the treatment of chronic HBV infection.
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