Gilead Sciences Inc., of Foster City, Calif., reported results from a large, multinational Phase III trial that demonstrated adefovir dipivoxil 10 mg significantly improved liver function and reduced levels of virus in patients with chronic hepatitis B virus (HBV) infection.
The data from Study 437 were presented at the 52nd annual Meeting of the American Association for the Study of Liver Diseases in Dallas.
Forty-eight week data from Study 437 demonstrated that patients with chronic HBV infection who received adefovir dipivoxil 10 mg once daily as monotherapy experienced statistically significant improvements in liver histology, reductions in HBV DNA and ALT levels, and a higher rate of seroconversion compared to patients given placebo. Change in liver histology is an important marker of disease progression in patients with chronic HBV infection, while HBV DNA and ALT levels are indicators of disease severity.
During the first year, 172 patients were randomized to receive adefovir dipivoxil 10 mg, 173 to receive adefovir dipivoxil 30 mg and 170 to receive placebo in the double-blind, placebo-controlled trial.
For patients with assessable baseline biopsies, improvement in liver histology was observed in 53 percent of patients treated with adefovir dipivoxil 10 mg (n=168), compared to 25 percent of placebo-treated patients (n=161), as measured by liver biopsies (p< 0.001). Seroconversion was observed in 12 percent of patients, compared to 6 percent of patients on placebo (p=0.049).
In other news released at the Dallas conference:
¿ BioMedicines Inc., of Alameda, Calif., reported positive results from two Phase II trials employing the company¿s omega interferon for the treatment of patients chronically infected with the hepatitis C virus. In an open-label European study, antiviral activity was assessed by measuring blood levels of HCV RNA and by liver enzyme testing. The interim results show that omega interferon can reduce HCV to undetectable levels in interferon-naive patients having any of the four major HCV genotypes. In a U.S. study, within 48 hours of the initiation of treatment with omega interferon, HCV RNA fell sharply in all patients, and in some to undetectable levels.
¿ Celgene Corp., of Warren, N.J., presented preclinical data on three of its small-molecule JNK (c-Jun N-terminal kinase) inhibitors. The study, conducted by Celgene and collaborators at the University of North Carolina at Chapel Hill, determined that over-activation of the JNK pathway following liver ischemia-reperfusion injury contributes to liver damage, involving cell death (apoptosis and necrosis). In the study, Celgene¿s small-molecule JNK inhibitors blocked liver damage and significantly enhanced survival in an in vivo model of liver ischemia-reperfusion injury.
¿ Enzo Biochem Inc., of New York, said that based on results of its Phase II study of EHT899 for patients with chronic active hepatitis B, it plans to initiate a multicenter, double-blind, randomized study of the product. Investigators conducting the Phase II trial reported that among the 42 patients, a dramatic improvement was observed in key liver necroinflammatory scores, with 33 percent of the subjects showing improvement. The study showed a reduction in the viral load and liver inflammation, a decrease in liver enzymes circulating in the blood and/or an enhancement of antiviral T-cell response. The results were presented at the American Association for the Study of Liver Diseases.
¿ ICN Pharmaceuticals Inc., of Costa Mesa, Calif., presented preclinical research on Viramidine that showed it may be more effective with fewer side effects than ribavirin. Ribavirin is part of a combination therapy to treat hepatitis C. New data on Levovirin also were presented. Findings revealed Viramidine potentially is safer because it targets the liver better than ribavirin. Viramidine is a next-generation analogue of ribavirin, as is Levovirin, which has been licensed to Roche Diagnostics Corp., a division of F. Hoffmann-La Roche Ltd., of Basel, Switzerland.
¿ InterMune Inc., of Brisbane, Calif., released positive interim results from a Phase IV trial comparing the use of Infergen (interferon alfacon-1) plus ribavirin to the use of interferon alfa-2b plus ribavirin (Rebetron) for the treatment of chronic hepatitis C infections. Patients treated with Infergen in combination with ribavirin achieved a sustained virologic response (SVR) of 56 percent compared with an SVR of 31 percent in patients treated with Rebetron.
¿ Maxim Pharmaceuticals Inc., of San Diego, reported 72-week results from its completed pilot study evaluating Ceplene (histamine dihydrochloride) in combination with interferon-alpha and ribavarin in the treatment of chronic hepatitis C patients who were nonresponsive to previous therapy. At this point, sustained complete viral response was observed in 28 percent, or five of 18, of patients in the study, and in 38 percent of evaluable patients, or patients who completed at least four weeks of therapy.
¿ Schering-Plough Corp., of Kenilworth, N.J., reported results of several clinical studies on PEG-Intron (peginterferon alfa-2b) Powder for Injection in combination with Rebetol (ribavirin) capsules for the treatment of chronic hepatitis C. Data indicated that PEG-Intron and Rebetol combination therapy reduces the rate of fibrosis progression in patients with chronic HCV. Researchers pooled data from four randomized studies involving 3,010 previously untreated patients with pre- and post-treatment biopsies who received one of 10 different regimens utilizing either standard or pegylated alpha interferon and ribavirin. While all regimens reduced fibrosis progression rates, PEG-Intron and Rebetol combination therapy showed the greatest improvement in liver necrosis and inflammation and the lowest rate of fibrosis worsening.