The following data were presented at American Association for the Study of Liver Disease meeting in Boston.
Arbutus Biopharma Corp., of Vancouver, British Columbia, presented preclinical results showing that capsid inhibitor AB-423 has a dual mode of action for treating hepatitis B virus (HBV), by inhibiting HBV DNA and cccDNA synthesis. Another presentation showed that second-generation RNAi agent ARB-1740 was shown to suppress multiple elements of HBV, including HBsAg, HBeAg, DNA, core antigen and all RNAs including the HBx transcript, as demonstrated in vivo. Arbutus also reported data from combination studies showing that AB-423 and ARB-1740 demonstrated synergistic activity against HBV rcDNA in vitro, as well as inhibition of HBV DNA and serum HBsAg in in vivo models. Triple combinations consisting of AB-423 plus ARB-1740 with direct-acting antiviral Baraclude (entecavir, Bristol-Myers Squibb Co.) or pegylated interferon provided the greatest reduction in serum HBV DNA.
Enanta Pharmaceuticals Inc., of Watertown, Mass., reported that 98 percent (n=102/104) of chronic hepatitis C virus (HCV)-infected patients with severe chronic kidney disease (CKD) achieved sustained virologic response following 12 weeks of treatment (SVR12) with partner North Chicago-based Abbvie Inc.’s investigational, pan-genotypic regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) in the primary intent-to-treat (ITT) analysis. In a modified ITT analysis, SVR12 was achieved in 100 percent (n=102/102) of severe CKD patients. That analysis excludes patients who did not achieve SVR for reasons other than virologic failure. The data are from the phase III EXPEDITION-4 study, evaluating patients with chronic HCV infection across all major genotypes (GT1-6) and severe CKD.
Gilead Sciences Inc., of Foster City, Calif., presented results from an open-label phase II trial of ASK1 inhibitor selonsertib (formerly GS-4997) alone or in combination with the monoclonal antibody simtuzumab in patients with nonalcoholic steatohepatitis, or NASH, and moderate to severe liver fibrosis (fibrosis stages F2 or F3). The data demonstrate regression in fibrosis that was, in parallel, associated with reductions in other measures of liver injury in patients treated with selonsertib for 24 weeks. Patients receiving selonsertib demonstrated improvements in several measures of liver disease severity, including fibrosis stage, progression to cirrhosis, liver stiffness (measured by magnetic resonance elastography) and liver fat content (measured by MRI-proton density fat fraction).
Replicor Inc., of Montreal, presented preliminary interim analysis from its latest REP 401 trial testing HBsAg release inhibitor REP 2139 and a REP 2139 derivative with improved plasma and tissue clearance (REP 2165) in combination with Viread (tenofovir disoproxil fumarate, or TDF, Gilead Sciences Inc.) and pegylated interferon alpha-2a (peg-IFN) in treatment-naïve patients with chronic HBeAg-negative hepatitis B virus (HBV) infection. Control patients receiving peg-IFN + TDF exhibited minimal antiviral response beyond suppression of serum HBV DNA, while patients receiving REP 2139 or REP 2139 in addition to peg-IFN and TDF experienced robust, multilog reductions in HBsAg, increased levels of circulating anti-HBsAg antibodies and serum transaminase flares indicating restored immune response in the liver.