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Hepatology. 2015 Oct;62(4):1013-23. doi: 10.1002/hep.27960. Epub 2015 Aug 10.

Alisporivir plus ribavirin, interferon free or in combination with pegylated interferon, for hepatitis C virus genotype 2 or 3 infection.

Author information

1
National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
2
INSERM U955, Créteil, France.
3
Medical University of Bialystok, Bialystok, Poland.
4
Institute of Liver and Biliary Sciences, New Delhi, India.
5
Klinikum der Albert-Ludwigs-Universität, Freiburg, Germany.
6
Prince of Songkla University, Songklanagarind Hospital, Hat-Yai, Songkhla, Thailand.
7
Kaohsiung Medical University, Chang-Ho Memorial Hospital, Kaohsiung, Taiwan.
8
School of Medicine, China Medical University, Taichung, Taiwan.
9
Bart's and The London School of Medicine, Queen Mary's University of London, London, United Kingdom.
10
Global Hospitals, Mumbai, India.
11
Hannover Medical School, Hannover, Germany.
12
Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
13
Beijing Novartis Pharma Co Ltd, Shanghai, China.
14
Novartis Institute of Biomedical Research, Emeryville, CA.
15
Novartis Institute of Biomedical Research, Cambridge, MA.
16
Novartis Pharma AG, Basel, Switzerland.

Abstract

Alisporivir is a cyclophilin inhibitor with pan-genotypic anti-hepatitis C virus (HCV) activity and a high barrier to viral resistance. The VITAL-1 study assessed alisporivir as interferon (IFN)-free therapy in treatment-naïve patients infected with HCV genotype 2 or 3. Three hundred forty patients without cirrhosis were randomized to: arm 1, alisporivir (ALV) 1,000 mg once-daily (QD); arm 2, ALV 600 mg QD and ribavirin (RBV); arm 3, ALV 800 mg QD and RBV; arm 4, ALV 600 mg QD and pegylated IFN (Peg-IFN); or arm 5, Peg-IFN and RBV. Patients receiving IFN-free ALV regimens who achieved rapid virological response (RVR) continued the same treatment throughout, whereas those with detectable HCV RNA at week 4 received ALV, RBV, and Peg-IFN from weeks 6 to 24. Overall, 300 patients received ALV-based regimens. In arm 1 to arm 4, the intent-to-treat rates of sustained virological response (SVR) 24 weeks after treatment (SVR24) were from 80% to 85%, compared with 58% (n = 23 of 40) with Peg-IFN/RBV. Per-protocol analysis showed higher SVR24 rates in patients who received ALV/RBV, IFN-free after RVR (92%; n = 56 of 61) than with ALV alone after RVR (72%; n = 13 of 18) or with Peg-IFN/RBV (70%; n = 23 of 33). Both RVRs and SVRs to ALV IFN-free regimens were numerically higher in genotype 3- than in genotype 2-infected patients. Viral breakthrough was infrequent (3%; n = 7 of 258). IFN-free ALV treatment showed markedly better safety/tolerability than IFN-containing regimens.

CONCLUSIONS:

ALV plus RBV represents an effective IFN-free option for a proportion of patients with HCV genotype 2 or 3 infections, with high SVR rates for patients with early viral clearance. Further investigations of ALV in IFN-free combination regimens with direct-acting antiviral drugs deserve exploration in future trials.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01215643.

PMID:
26118427
DOI:
10.1002/hep.27960
[Indexed for MEDLINE]

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