Clevudine (L-FMAU)

清照

Clevudine is biochemically similar to DFIAU, but does not appear to have the associated problems of mitochondrial toxicity and lactic acidosis production, at least in vitro. Experiments in the infected woodchuck model have shown this drug to be highly active at a dose of 10mg per kg once daily, producing a 9 log decrease in viral load with a dose dependent delay in the time to viral recrudescence.

An open label phase I / II dose escalation study is underway, with patients receiving either 10mg, 50mg or 100mg once daily for 28 days. 24 of 25 individuals have completed the study protocol Median DNA reduction at day 28 was 2.48, 2.74 and 2.95 log10 copies/mL respectively. Interestingly, 5 months after the end of treatment the median decrease in HBV DNA was 1.91 log10 copies/mL in the 10mg arm, and 2.07 log10 copies/mL among individuals receiving 50mg of clevudine. In individuals who received 100mg once daily, data was only available to week 8 (one month post therapy cessation) with 5 available patients demonstrating a continued HBV DNA fall greater than 3 log10 copies/mL.

Reference
Selected Highlights from Drug Development for Antiretroviral Therapies 2001 (Hep DART 2001) [Abstract 039]
December 16-20, 2001, Maui, Hawaii

清照

DAPD and Clevudine (L-FMAU) are nucleoside analog drugs that show potent anti-HBV activity in the laboratory. They also are effective against various HBV strains resistant to Epivir-HBV (lamivudine). DAPD also has anti-HIV activity, while L-FMAU does not. Both agents will proceed to clinical trials. The drugs are being developed by Triangle Pharmaceuticals.


Reference
Chin R and others. Two novel antiviral agents, DAPD and L-FMAU, which are active against wild type and lamivudine-resistant HBV. Abstract and oral presentation 1041 at the 50th Annual Meeting of the American Association for the Study of Liver Diseases. Dallas, Texas; November 5-9, 1999. Hepatology 30(4) Supp2, 421A

News Stories on Clevudine

Clevudine (L-FMAU) Shows Antiviral Activity and a Unique Post-Treatment Effect in a Phase I/II Dose-Escalating Trial in Patients with Chronic Hepatitis B
03/26/03

Combination Treatment with Coviracil (emtricitabine) Plus Clevudine with Interferon Gamma in the Woodchuck Model of Hepatitis B Infection
01/22/03

Mutual Agreement with Abbott Allows Triangle to Re-Acquire Full Rights to Develop Four Experimental Drugs: Coviracil for?Hepatitis B and HIV,  Clevudine for Hepatitis B and Amdoxovir for HIV
07/31/02

Clevudine - Update from Drug Development for Antiretroviral Therapies 2001 (Hep DART 2001)
02/04/02

OCD

Gilead's Clevudine (L-FMAU), Bristol-Myers Squibb's Entecavir and Idenix,'s Telbivudine are all in final stage, and those three companies believed to be the leading HBV drug factories for some time in the near future.