New treatments for genotype 1 chronic hepatitis C – focus on simeprevir

Figures & data

Figure 1 Structure of simeprevir.

Figure 2 PILLAR study design and results. SVR rates were measured at 24 weeks after the end of treatment.

Notes: RGT algorithm: all therapy of the SMV group was completed at week 24 if hepatitis C virus RNA was <25 IU/mL at week 4 and undetectable at weeks 12, 16, and 20. Data from Fried MW et al.²¹ In the control group, patients received PR (180 μg/week peginterferon; 1,000–1,200 mg/day ribavirin) for 48 weeks.
Abbreviations: PILLAR, Protease Inhibitor TMC435 Trial Assessing the Optimal Dose and Duration as Once-Daily Antiviral Regimen; PR, peginterferon plus ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response.

Figure 3 DRAGON study designs and results.

Notes: SVR rates were measured at 24 weeks after the end of treatment. RGT criteria: all therapy of the SMV group was completed at week 24 if hepatitis C virus RNA was <1.4 log₁₀ IU/mL at week 4 and undetectable at weeks 12, 16, and 20; otherwise PR (180 µg/week peginterferon α-2a; 600–1,000 mg/day ribavirin) was continued to week 48. In the control group, patients received PR for 48 weeks. Data from Hayashi et al.²²
Abbreviations: DRAGON, A Phase II Study of TMC435 in Patients with Chronic Hepatitis C; PR, peginterferon plus ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response.

Figure 4 SVR12 in four Phase III Japanese hepatitis C virus genotype 1 patients treated with (A and B) simeprevir and ribavirin plus peginterferon α-2a or (C) peginterferon α-2b. (A) CONCERTO-1 trials for treatment-naïve patients; (B) CONCERTO-2 and CONCERTO-3 trials for prior non-responders and prior relapsers, respectively; and (C) CONCERTO-4 trials for treatment-naïve patients, prior non-responders, and prior relapsers. Data from Hayashi et al,²⁵ Izumi et al,²⁶ and Suzuki et al.²⁷

Abbreviations: CONCERTO-1, A Study of the Efficacy of Combination Therapy Including Simeprevir (TMC435) in the Treatment of Genotype 1 Hepatitis C; CONCERTO-2/3, A Study of the Efficacy of Retreatment with Simeprevir (TMC435) in the Treatment of Genotype 1 Hepatitis C; CONCERTO-4, A Study of the Efficacy of Combination Therapy with Simeprevir (TMC435), Peginterferon α-2b, and Ribavirin in the Treatment of Genotype 1 Hepatitis C; SVR12, sustained virologic response 12 weeks after the end of treatment; wks, weeks.

FriedMWButiMDoreGJOnce-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR studyHepatology20135861918192923907700

 PubMed Web of Science ®Google Scholar

HayashiNSetoCKatoMKomadaYGotoSOnce-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON studyJ Gastroenterol201449113814724005956

 PubMed Web of Science ®Google Scholar

HayashiNIzumiNKumadaHSimeprevir with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trialJ Hepatol Epub201449

 Web of Science ®Google Scholar

IzumiNHayashiNKumadaHOnce-daily simeprevir with peginterferon and ribavirin for treatment-experienced HCV genotype 1-infected patients in Japan: the CONCERTO-2 and CONCERTO-3 studiesJ Gastroenterol201449594195324626851

 PubMed Web of Science ®Google Scholar

SuzukiFHayashiNGotoSKumadaHSimeprevir with Peginterferon alpha-2b/Ribavirin for hepatitis C genotype 1 patients: the CONCERTO-4 studyKanzo201454suppl1A157 Japanese

 Google Scholar