Description
Telbivudine is an investigational new drug demonstrating marked antiviral activity against the hepatitis B virus (HBV) and is being evaluated clinically for treatment of patients with chronic hepatitis B. Telbivudine, the generic name for L-deoxythymidine (LdT), has demonstrated high selectivity for HBV. In clinical trials and non-clinical studies, telbivudine has demonstrated virtually no activity against other viruses or infectious pathogens, and has a favorable safety profile. In our phase III clinical trials, telbivudine is dosed orally once daily in a tablet form.
Mode of Action
Telbivudine is an HBV-specific nucleoside analog. Telbivudine specifically targets the viral DNA polymerase enzyme that is responsible for HBV replication. Telbivudine has demonstrated no activity against other viruses that cause human disease. This specificity will permit the treatment of persons co-infected with other viruses without an increased risk of contributing to resistance development for HIV or other viruses. Idenix believes these attributes will contribute to the value of this new agent in managing the different categories of patients with hepatitis B.
The chemical structure of telbivudine is the mirror image of thymidine, a naturally occurring nucleoside building block of DNA. We believe the HBV polymerase mistakenly recognizes telbivudine as if it were natural thymidine, incorporating it into HBV DNA resulting in chain termination and potent inhibition of viral replication. The more selective polymerase enzymes of the human body do not appreciably recognize or interact with telbivudine, thus protecting normal cellular functions from toxic effects. We believe that this high level of selectivity is responsible for the favorable safety of telbivudine in clinical trials.
CLINICAL TRIAL RESULTS
In a recently completed phase IIb clinical trial, one year of telbivudine treatment reduced HBV in the blood to undetectable levels (i.e. less than 200 particles/mL) in 61 percent of patients, significantly more than the 32 percent of patients who achieved this result with lamivudine, the current standard of care (p<0.05). The high degree of viral suppression provided by telbivudine is among the most significant of anti-HBV therapeutic agents in development. Additionally, in this clinical trial, serum ALT, a marker of HBV-related liver inflammation, normalized in 86 percent of telbivudine-treated patients, significantly greater than the 63 percent in the lamivudine group (p<0.05). We believe that this clinical trial demonstrated the importance of maximizing early viral suppression for improving clinical outcome. In all treatment groups, patients with the greatest degree of viral suppression early in the course of therapy (by 24 weeks) had the highest rates of seroconversion (a predictor of durable resolution of disease), ALT normalization (reduction of liver inflammation), and the lowest rate of drug resistance.
Safety & Tolerability
Telbivudine appears to be well tolerated in clinical trials. To date, there has been no pattern of patient discontinuations due to serious adverse events.
Clinical Development
An international phase III clinical trial, known as “the GLOBE study”, is ongoing and fully enrolled, including more than 1,350 patients and approximately 135 clinical centers. It is expected that the initial phase of this clinical trial will be completed in 2005, with submission of worldwide registration applications expected to begin by year-end 2005.
From http://www.idenix.com/products/telbivudine.html | 
发表于 2005-1-31 20:33
