Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients

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Hepatology. 2010 Aug 19. [Epub ahead of print]

Antiviral activity of narlaprevir combined with ritonavir and pegylated

interferon in chronic hepatitis C patients.

de Bruijne J, Bergmann JF, Reesink HW, Weegink CJ, Molenkamp R, Schinkel J, Tong

X, Li J, Treitel MA, EA, van Lier JJ, van Vliet AA, Janssen HL, de Knegt

RJ.

Department of Gastroenterology and Hepatology, Academic Medical Center,

Amsterdam, The Netherlands.

Abstract

Narlaprevir (SCH 900518) is a potent inhibitor of the hepatitis C virus (HCV)

nonstructural protein 3 serine protease that is primarily metabolized by the

cytochrome P450-3A4 system. In order to explore the use of ritonavir-based

pharmacokinetic enhancement of an HCV protease inhibitor, this study

investigated the safety, tolerability, pharmacokinetics, and antiviral activity

of narlaprevir (with or without ritonavir) administered as monotherapy and as

combination therapy with pegylated interferon-α-2b (PEG-IFN-α-2b) to HCV

genotype 1-infected patients. This was a randomized, placebo-controlled,

two-period, blinded study in 40 HCV genotype 1-infected patients (naïve and

treatment-experienced). In period 1, narlaprevir was administered for 7 days as

800 mg three times daily without ritonavir or 400 mg twice daily with 200 mg

ritonavir twice daily. In period 2, after a 4-week washout, the same dose and

regimen of narlaprevir was administered in combination with PEG-IFN-α-2b for 14

days. Upon completion of period 2, all patients initiated PEG-IFN-α-2b and

ribavirin treatment. A rapid and persistent decline in plasma HCV-RNA was

observed in both treatment-experienced and treatment-naïve patients during

period 1, with a mean viral load decline of at least 4 log(10) in all treatment

groups. A high percentage of both treatment-experienced (50%) and

treatment-naïve (≥60%) patients had undetectable HCV-RNA (<25 IU/mL) after

period 2. Standard of care resulted in sustained virological response (SVR)

rates of 38% and 81% in treatment-experienced and treatment-naïve patients,

respectively. Narlaprevir (with or without ritonavir) alone or in combination

with PEG-IFN-α-2b was safe and well tolerated. Conclusion: Narlaprevir

administration resulted in a robust HCV-RNA decline and high SVR rates when

followed by standard of care in both treatment-experienced and treatment-naïve

HCV genotype 1-infected patients. (HEPATOLOGY 2010.

PMID: 20938912 [PubMed - as supplied by publisher]