摘要
Nucleotide compounds like sofosbuvir,acyclovir,and tenofovir have proven to be amongst the most potent orally available antiviral treatments.These drugs exhibit high efficacy and a wide therapeutic index,with demonstrated utility in a number of chronic viral infections.The approval of SovaldiTM,brand name for sofosbuvir,by the U.S.Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment.Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977.It was subsequently acquired and advanced through phase 3 development by Gilead Sciences,Inc.In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious.Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR),curing patients in excess of 80% in all genotypes and >90% in treatment-na(i)ve subjects being administered combination therapy with other agents.Harvoni~ is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet,and it has demonstrated high SVR rates in patients infected with HCV genotype 1,without the need for exogenous interferon and/or ribavirin.Here,we discuss the discovery,development,pharmacologic characterization,and results from the phase 3 trials of sofosbuvir.Hepatitis C is a chronic disease,for which most patients have been undiagnosed,are unwilling to start treatment,or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy.Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care,thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines.
Nucleotide compounds like sofosbuvir,acyclovir,and tenofovir have proven to be amongst the most potent orally available antiviral treatments.These drugs exhibit high efficacy and a wide therapeutic index,with demonstrated utility in a number of chronic viral infections.The approval of SovaldiTM,brand name for sofosbuvir,by the U.S.Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment.Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977.It was subsequently acquired and advanced through phase 3 development by Gilead Sciences,Inc.In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious.Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR),curing patients in excess of 80% in all genotypes and >90% in treatment-na(i)ve subjects being administered combination therapy with other agents.Harvoni~ is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet,and it has demonstrated high SVR rates in patients infected with HCV genotype 1,without the need for exogenous interferon and/or ribavirin.Here,we discuss the discovery,development,pharmacologic characterization,and results from the phase 3 trials of sofosbuvir.Hepatitis C is a chronic disease,for which most patients have been undiagnosed,are unwilling to start treatment,or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy.Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care,thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines.
