Chronic hepatitis C genotype 5

Also known as: Chronic viral hepatitis C / Chronic hepatitis C / Hepatitis C, Chronic

DrugDrug NameDrug Description
DB13879GlecaprevirGlecaprevir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS3/4A protease inhibitor that targets the the viral RNA replication. In combination with [DB13878], glecaprevir is a useful therapy for patients who experienced therapeutic failure from other NS3/4A protease inhibitors. It demonstrates a high genetic barrier against resistance mutations of the virus. In cell cultures, the emergence of amino acid substitutions at NS3 resistance-associated positions A156 or D/Q168 in HCV genotype 1a, 2a or 3a replicons led to reduced susceptibility to glecaprevir [FDA Label]. The combinations of amino acid substitutions at NS3 position Y65H and D/Q168 also results in greater reductions in glecaprevir susceptibility, and NS3 Q80R in genotype 3a patients also leads to glecaprevir resistance [FDA Label]. Glecaprevir is available as an oral combination therapy with [DB13878] under the brand name Mavyret. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis [L940]. Mavyret is also indicated for HCV genotype 1-infected patients who have been previously treated with regimens either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both [L940]. Hepatitis C viral infection often leads to decreased liver function and subsequent liver failure, causing a significantly negative impact on the patients' quality of life. The ultimate goal of the combination treatment is to achieve sustained virologic response (SVR) and cure the patients from the infection. In clinical trials, this combination therapy achieved SVR12 rate, or undetectable Hepatitis C for twelve or more weeks after the end of treatment, of ≥93% across genotypes 1a, 2a, 3a, 4, 5 and 6 [FDA Label].
DB09027LedipasvirLedipasvir is a direct acting antiviral (DAA) medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as ledipasvir. More specifically, ledipasvir is an inhibitor of the Hepatitis C Virus (HCV) Non-Structural Protein 5A (NS5A), which is required for viral RNA replication and assembly of HCV virions. Although its exact mechanism of action is unknown, it is postulated to prevent hyperphosphorylation of NS5A which is required for viral protein production. It is effective against genotypes 1a, 1b, 4a, and 5a and with a lesser activity against genotypes 2a and 3a of HCV. Ledipasvir and other direct acting antivirals are very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance [A19593]. This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend ledipasvir as a first line therapy option in combination with [DB08934] for the treatment of HCV genotypes 1a, 1b, 4, 5, and 6 [L852]. Treatment with ledipasvir is used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Treatment with direct acting antivirals such as ledipasvir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [A19635]. Since 2014, ledipasvir has been available as a fixed dose combination product with [DB08934] (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without [DB00811] depending on the level of liver damage or cirrhosis [FDA Label]. When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment [FDA Label]. Its use has also proven successful in the treatment of HCV in patients co-infected with HIV [A19627].
DB13878PibrentasvirPibrentasvir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS5A inhibitor that targets the the viral RNA replication and viron assembly. In combination with [DB13879], pibrentastiv is a useful therapy for patients who experienced therapeutic failure from other NS5A inhibitors. In cell cultures, the emergence of amino acid substitutions at known NS5A inhibitor resistance-associated positions in HCV genotype 1a, 2a or 3a replicons led to reduced susceptibility and resistance to pibrentasvir [FDA Label]. These resistance-associated amino acid substitutions included Q30D/deletion, Y93D/H/N or H58D +Y93H in genotype 1a replicons, F28S + M31I or P29S + K30G in genotype 2a replicons, and Y93H in genotype 3a replicons. Individual NS5A amino acid substitutions that reduced susceptibility to pibrentasvir include M28G or Q30D in a genotype 1a replicon and P32-deletion in a genotype 1b replicon [FDA Label]. Pibrentasvir is available as an oral combination therapy with [DB13879] under the brand name Mavyret. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis [L940]. Mavyret is also indicated for HCV genotype 1-infected patients who have been previously treated with regimens either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both [L940]. Hepatitis C viral infection often leads to decreased liver function and subsequent liver failure, causing a significantly negative impact on the patients' quality of life. The ultimate goal of the combination treatment is to achieve sustained virologic response (SVR) and cure the patients from the infection. In clinical trials, this combination therapy achieved SVR12 rate, or undetectable Hepatitis C for twelve or more weeks after the end of treatment, of ≥93% across genotypes 1a, 2a, 3a, 4, 5 and 6 [FDA Label].
DB08934SofosbuvirSofosbuvir (tradename Sovaldi) is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as sofosbuvir. As a prodrug nucleotide analog, Sofosbuvir is metabolized into its active form as the antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate (also known as GS-461203), which acts as a defective substrate for NS5B (non-structural protein 5B) [synthesis]. NS5B, an RNA-dependent RNA polymerase, is essential for the transcription of Hepatitis C viral RNA and for its high replicative rate and genetic diversity [A19594]. Sofosbuvir and other direct acting antivirals are therefore very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance [A19593]. This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Sofosbuvir as first line therapy in combination with other antivirals for all six genotypes of Hepatitis C [L852]. Depending on the genotype, sofosbuvir is often used in combination with other antivirals such as [DB09027], [DB11613], [DB09102], [DB06290], [DB11574], [DB11575], [DB00811], [DB00008], or [DB00022] with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [A19626]. Treatment with direct acting antivirals such as sofosbuvir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [A19635]. Since 2014, sofosbuvir has been available as a fixed dose combination product with [DB09027] (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without [DB00811] depending on the level of liver damage or cirrhosis [FDA Label]. When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment [A7535]. Its use has also proven successful in the treatment of HCV in patients co-infected with HIV [A19627]. Sofosbuvir is also available as a fixed dose combination product with [DB11613] as the commercially available product Epclusa. First approved in June 2016, Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. Epclusa is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis [L852]. Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV [L852, A19626]. Notably, sofosbuvir has come under intense scrutiny since its release to market in 2013. With the price per pill set at $1000, a 12-week treatment can cost upwards of $84,000 per patient [A19636].
DB11613VelpatasvirVelpatasvir is a Direct-Acting Antiviral (DAA) medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [L852]. Velpatasvir acts as a defective substrate for NS5A (Non-Structural Protein 5A), a non-enzymatic viral protein that plays a key role in Hepatitis C Virus replication, assembly, and modulation of host immune responses [A19175]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as velpatasvir. Notably, velpatasvir has a significantly higher barrier to resistance than the first generation NS5A inhibitors, such as [DB09027] and [DB09102], making it a highly potent and reliable alternative for treatment of chronic Hepatitis C [A19637]. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Velpatasvir as first line therapy in combination with sofosbuvir for all six genotypes of Hepatitis C [L852]. Velpatasvir is currently only available within a fixed dose combination product as Epclusa with [DB08934], another direct acting antiviral. Goals of therapy for Epclusa include the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality and risk of requiring a liver transplant [A19626]. Since June 2016, Velpatasvir has been available as a fixed dose combination product with [DB08934], as the commercially available product Epclusa. Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. It is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis and a high barrier to resistance [L852]. Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV [L852, A19626].
DrugDrug NameTargetType
DB13879GlecaprevirCYP3Aenzyme
DB13879GlecaprevirUDP-glucuronosyltransferase 1-1enzyme
DB13879GlecaprevirMultidrug resistance protein 1transporter
DB13879GlecaprevirATP-binding cassette sub-family G member 2transporter
DB13879GlecaprevirSolute carrier organic anion transporter family member 1B1transporter
DB13879GlecaprevirSolute carrier organic anion transporter family member 1B3transporter
DB13879GlecaprevirNS3 proteasetarget
DB09027LedipasvirNonstructural protein 5Atarget
DB09027LedipasvirMultidrug resistance protein 1transporter
DB09027LedipasvirATP-binding cassette sub-family G member 2transporter
DB13878PibrentasvirNonstructural Protein 5A (NS5A)target
DB13878PibrentasvirCYP3Aenzyme
DB13878PibrentasvirUDP-glucuronosyltransferase 1-1enzyme
DB13878PibrentasvirMultidrug resistance protein 1transporter
DB13878PibrentasvirATP-binding cassette sub-family G member 2transporter
DB13878PibrentasvirSolute carrier organic anion transporter family member 1B1transporter
DB13878PibrentasvirSolute carrier organic anion transporter family member 1B3transporter
DB08934SofosbuvirMultidrug resistance protein 1transporter
DB08934SofosbuvirATP-binding cassette sub-family G member 2transporter
DB08934SofosbuvirRNA-dependent RNA-polymerasetarget
DB08934SofosbuvirLysosomal protective proteinenzyme
DB08934SofosbuvirCarboxylesteraseenzyme
DB08934SofosbuvirHistidine triad nucleotide-binding protein 1enzyme
DB08934SofosbuvirUMP-CMP kinaseenzyme
DB08934SofosbuvirNucleoside diphosphate kinase Aenzyme
DB11613VelpatasvirCytochrome P450 2B6enzyme
DB11613VelpatasvirCytochrome P450 2C8enzyme
DB11613VelpatasvirCytochrome P450 3A4enzyme
DB11613VelpatasvirNonstructural Protein 5A (NS5A)target
DB11613VelpatasvirMultidrug resistance protein 1transporter
DB11613VelpatasvirATP-binding cassette sub-family G member 2transporter
DB11613VelpatasvirSolute carrier organic anion transporter family member 1B1transporter
DB11613VelpatasvirSolute carrier organic anion transporter family member 1B3transporter
DB11613VelpatasvirSolute carrier organic anion transporter family member 2B1transporter
DrugDrug NamePhaseStatusCount