Experimental Drugs for HBV Infection7

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Adefovir Dipivoxil



Adefovir dipivoxil is an experimental drug being developed by Gilead Sciences. It is an oral drug from a class of antiviral compounds known as nucleotide analogs. It also has activity against HIV. New data demonstrate the potent antiviral activity of adefovir dipivoxil against the hepatitis B virus (HBV) in chronically infected patients. According to Gilead, 12 weeks of therapy with adefovir dipivoxil rapidly reduced blood plasma levels of HBV in patients by up to 99.99 percent (4.0 log). Additional results show that a 12-week course of therapy is associated with loss of the hepatitis B "e" antigen from the bloodstream and seroconversion, and with the development of anti-HBV antibodies by the immune system.



Adefovir Dipivoxil Rapidly Reduces HBV DNA



In one study, 53 patients with chronic HBV who had elevated blood levels of liver enzyme markers that indicate liver disease (ALT) were randomly given a placebo or a 5 mg, 30 mg or 60 mg dose of adefovir dipivoxil once daily for 12 weeks. Sixty-seven percent of patients who received the 30 mg dose exhibited viral suppression that fell below the detectable limits of the DNA test. When quantified with a more sensitive assay (PCR), the median reduction of HBV DNA was found to be 99.99 percent or 4.0 log. These results were statistically significant. Similar results were seen in the 60 mg treatment arm, while a median decrease in HBV DNA of more than 90 percent was seen in the 5 mg dose arm.



Treatment with adefovir dipivoxil also was associated with seroconversion. Seroconversion is defined as the disappearance of the hepatitis B "e" antigen (HBe-antigen), a marker of HBV replication, and the appearance of antibodies specific for this antigen (HBe-antibody). After 24 weeks of follow-up, 27 percent of patients (8 of 30) in the 30 and 60 mg dose arms lost HBe-antigen, and 20 percent (6 of 30) seroconverted. The number of patients who lost HBe-antigen and seroconverted were equal in the 30 mg and 60 mg dose groups. None of the patients who received placebo seroconverted, or lost HBe- or HBs-antigen. It was also reported that adefovir dipivoxil has significant activity against all known clinically relevant Epivir HBV- and Famvir-resistant HBV strains.



› Preliminary Results of Phase III Study of Adefovir Dipivoxil in Precore Mutant Chronic Hepatitis B Virus (HBV) Infection



› Adefovir Dipivoxil Shows Benefits for Patients Co-Infected with HIV and HBV



› Adefovir Dipivoxil has Potent Effect on Drug-Resistant HBV



› Results with Adefovir are Promising for Chronic Hepatitis B Infection