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

Norio Hayashi, Chiharu Seto, Mai Kato, Yuji Komada, Shoichiro Goto, Norio Hayashi, Chiharu Seto, Mai Kato, Yuji Komada, Shoichiro Goto

Abstract

Background: Efficacy, safety and pharmacokinetics of simeprevir (TMC435), a once-daily, noncovalent, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in combination with peginterferon α-2a/ribavirin (PegIFNα-2a/RBV) for treatment-naïve, HCV genotype 1-infected patients in Japan.

Methods: In a multicenter, randomized clinical trial in Japan, ninety-two patients received either simeprevir (50 or 100 mg QD) for 12 or 24 weeks with PegIFNα-2a/RBV for 24 or 48 weeks (according to response-guided therapy [RGT] criteria), or PegIFNα-2a/RBV for 48 weeks (PR48 group).

Results: Compared with the PR48 group, plasma HCV RNA reductions in the simeprevir groups were rapid and more substantial (Week 4: -5.2, -5.2 and -2.9 log10IU/mL for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively). High rapid virologic response rates (83, 90, and 8 % for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively) led to high sustained virologic response rates (77-92 %, compared with 46 % for PR48). All but one of the simeprevir-treated patients were eligible to complete treatment after 24 weeks (RGT). Relapse rates in simeprevir-treated patients were low (8-17 %, compared with 36 % for the PR48 group). There were no notable differences in the safety profile between the simeprevir and PR48 groups.

Conclusions: The addition of simeprevir QD to PegIFNα-2a/RBV, as compared with PegIFNα-2a/RBV alone, demonstrated potent antiviral activity and significantly improved the rates of sustained virologic response, with a shortened 24-week treatment duration, in treatment-naive patients infected with HCV genotype 1 in Japan. Simeprevir was generally safe and well tolerated. (ClinicalTrials.gov number, NCT00996476).

Figures

Fig. 1
Fig. 1
Mean change from baseline in plasma HCV RNA through week 24. HCV hepatitis C virus, PR peginterferon + ribavirin, SD standard deviation, SMV simeprevir
Fig. 2
Fig. 2
Sustained virologic response rates (SVR24). PR peginterferon + ribavirin, SMV simeprevir
Fig. 3
Fig. 3
Mean hemoglobin and total bilirubin in patient plasma through week 48. Total bilirubin ULN = 17.1 μmol/L. Scr screening visit, BL baseline visit, PR peginterferon + ribavirin, SD standard deviation, SMV simeprevir, ULN upper limit of normal

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