Atea is developing bemnifosbuvir in combination with ruzasvir for the treatment of HCV. As single agents, both bemnifosbuvir and ruzasvir have demonstrated potent pan-genotypic antiviral activity against HCV. Ruzasvir is an investigational oral, pan genotypic NS5A inhibitor for the treatment of chronic HCV infection that was licensed from Merck. Ruzasvir is a Phase 2-ready NS5A inhibitor that has already been evaluated by Merck in over 1,200 HCV-infected patients.
A combination of bemnifosbuvir and ruzasvir has the potential to offer a differentiated short duration, pan-genotypic protease-sparing regimen for HCV-infected patients with or without cirrhosis. For patients with decompensated cirrhosis, a life-threatening stage of liver disease, the combination of bemnifosbuvir and ruzasvir may have the potential to treat these patients without the co-administration of ribavirin, which can cause a wide range of serious side effects.
Atea plans to initiate a Phase 2 trial of bemnifosbuvir in combination with ruzasvir in treatment-naïve, HCV-infected patients either without cirrhosis or with compensated cirrhosis.
Results from this study are intended to support future larger studies of bemnifosbuvir in combination with ruzasvir in broad patient populations.
The combination of bemnifosbuvir and ruzasvir demonstrated in vitro synergy in HCV GT1b replicon assays (Huh-luc/neo-ET), where HCV replicon cells were treated with multiple concentrations of AT-511, the free base of bemnifosbuvir, and ruzasvir either alone or in combination. As shown in the figure below, these experiments demonstrated that the combination resulted in substantially greater inhibition of HCV replication than either agent alone, suggesting a synergistic antiviral effect between the two inhibitors.