50 Activity of Telaprevir Alone or in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Genotype 2 and 3 Hepatitis-C Patients: Interim Results of Study C209

Foster, G.R.; Hézode, Christophe; Bronowicki, Jean–Pierre; Carosi, G.; Weiland, O; Verlinden, L.; Heeswijk, Rolf van; Vangeneugden, Tony; Picchio, Gastón; Beumont–Mauviel, Maria

doi:10.1016/s0168-8278(09)60052-0

Cited by 34 publications

(25 citation statements)

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“…HCV SPRINT-1 study Naı¨ve treatment-naïve [27,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][93][94][95][96][97][98] assessed the safety and efficacy of boceprevir, an oral inhibitor of HCV-NS3 protease, plus pegIFN alpha-2b and ribavirin (Table 4). SVR was significantly increased in the 28-and 48-week boceprevir arms compared to pegIFN alpha-2b and RBV control.…”

Section: Boceprevirmentioning

confidence: 99%

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New antiviral therapies for chronic hepatitis C

2010

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Chronic hepatitis C is an important health issue worldwide. The current standard therapy is based on a combination of pegylated-interferon (pegIFN) and ribavirin (RBV), but this treatment leads to only ~50% sustained virological response (SVR) in patients with HCV genotype 1 and high viral loads, who were mostly null-responders or relapsers. Among HCV genotypes other than HCV genotype 1, especially HCV genotype 4 patients show only 40-70% SVR by this treatment. Although new drugs also depend on the combination of pegIFN and RBV, it appears that these drugs improve not only rapid virological response (RVR) but also early virological response, leading to SVR in these patients. In the near future, we predict higher SVR rates in chronic hepatitis C patients treated with these new drugs.

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Section: Boceprevirmentioning

confidence: 99%

“…Telaprevir demonstrated substantial antiviral activity against HCV genotype 2, while its activity against HCV genotype 3 was limited. Additional investigations of telaprevir for the treatment of HCV genotype 2 infection are needed [39].…”

Section: Telaprevir (Vx-950)mentioning

confidence: 99%

New antiviral therapies for chronic hepatitis C

2010

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“…From a therapeutic perspective, in genotype 3-infected patients sustained virologic response (SVR) rates are up to 66-80% and appears intermediate between those registered in genotype 2 and genotype 1 [7]. Finally, it should be mentioned that the protease inhibitors, telaprevir, and boceprevir, are mainly active against genotypes 1 and 2, and less active against genotypes 3 and 4 [8,9], thus implying that the combination of Peg-interferon alfa and ribavirin may remain the key treatment option for patients infected with HCV genotype 3.…”

Section: Introductionmentioning

confidence: 99%

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3

Mangia

Bandiera

Montalto

et al. 2010

Journal of Hepatology

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“…Pegylated IFN-␣ and ribavirin treatment can achieve SVR rates of 70 to 80% in genotype 2-or 3-infected patients, but the SVR rate is less than 50% for genotype 1-or 4-infected patients (4,5). Telaprevir is not active against genotypes 3 and 4 of HCV (21,22) and is approved only for treatment of genotype 1-infected patients. There is a clear need for agents with pangenotypic activity due to the diversity of HCV genotypes and their differential responses to current therapies.…”

mentioning

confidence: 99%

In Vitro Characterization of GSK2485852, a Novel Hepatitis C Virus Polymerase Inhibitor

Voitenleitner

Crosby

Walker

et al. 2013

Antimicrob Agents Chemother

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; GlaxoSmithKline, Collegeville, Pennsylvania, USA c GSK2485852 (referred to here as GSK5852) is a hepatitis C virus (HCV) NS5B polymerase inhibitor with 50% effective concentrations (EC 50 s) in the low nanomolar range in the genotype 1 and 2 subgenomic replicon system as well as the infectious HCV cell culture system. We have characterized the antiviral activity of GSK5852 using chimeric replicon systems with NS5B genes from additional genotypes as well as NS5B sequences from clinical isolates of patients infected with HCV of genotypes 1a and 1b. The inhibitory activity of GSK5852 remained unchanged in these intergenotypic and intragenotypic replicon systems. GSK5852 furthermore displays an excellent resistance profile and shows a <5-fold potency loss across the clinically important NS5B resistance mutations P495L, M423T, C316Y, and Y448H. Testing of a diverse mutant panel also revealed a lack of cross-resistance against known resistance mutations in other viral proteins. Data from both the newer 454 sequencing method and traditional population sequencing showed a pattern of mutations arising in the NS5B RNA-dependent RNA polymerase in replicon cells exposed to GSK5852. GSK5852 was more potent than HCV-796, an earlier inhibitor in this class, and showed greater reductions in HCV RNA during long-term treatment of replicons. GSK5852 is similar to HCV-796 in its activity against multiple genotypes, but its superior resistance profile suggests that it could be an attractive component of an all-oral regimen for treating HCV.

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50 Activity of Telaprevir Alone or in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Genotype 2 and 3 Hepatitis-C Patients: Interim Results of Study C209

Cited by 34 publications

References 0 publications

New antiviral therapies for chronic hepatitis C

New antiviral therapies for chronic hepatitis C

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3

In Vitro Characterization of GSK2485852, a Novel Hepatitis C Virus Polymerase Inhibitor

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