Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

S Zeuzem; R Flisiak; J M Vierling; W Mazur; G Mazzella; S Thongsawat; D Abdurakhmanov; N Van Kính; P Calistru; J Heo; C Stanciu; M Gould; M Makara; S-J Hsu; P Buggisch; D Samuel; D Mutimer; B Nault; M Merz; W Bao; L H Griffel; C Brass; N V Naoumov; ESSENTIAL II Study Group

doi:10.1111/apt.13342

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

S Zeuzem, R Flisiak, J M Vierling, W Mazur, G Mazzella, S Thongsawat, D Abdurakhmanov, N Van Kính, P Calistru, J Heo, C Stanciu, M Gould, M Makara, S-J Hsu, P Buggisch, D Samuel, D Mutimer, B Nault, M Merz, W BaoL H Griffel, C Brass, N V Naoumov, ESSENTIAL II Study Group

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance.

AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection.

METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.

RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.

CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.

Original language	English
Pages (from-to)	829-44
Number of pages	16
Journal	Alimentary Pharmacology & Therapeutics
Volume	42
Issue number	7
DOIs	https://doi.org/10.1111/apt.13342
Publication status	Published - Oct 2015

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Zeuzem, S., Flisiak, R., Vierling, J. M., Mazur, W., Mazzella, G., Thongsawat, S., Abdurakhmanov, D., Van Kính, N., Calistru, P., Heo, J., Stanciu, C., Gould, M., Makara, M., Hsu, S-J., Buggisch, P., Samuel, D., Mutimer, D., Nault, B., Merz, M., ... ESSENTIAL II Study Group (2015). Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II). Alimentary Pharmacology & Therapeutics, 42(7), 829-44. https://doi.org/10.1111/apt.13342

@article{e474dae56b05447d87e4f5433e0ceb72,

title = "Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-na{\"i}ve patients with chronic HCV genotype 1 infection (ESSENTIAL II)",

abstract = "BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance.AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-na{\"i}ve patients with chronic HCV genotype 1 infection.METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-na{\"i}ve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.",

author = "S Zeuzem and R Flisiak and Vierling, {J M} and W Mazur and G Mazzella and S Thongsawat and D Abdurakhmanov and {Van K{\'i}nh}, N and P Calistru and J Heo and C Stanciu and M Gould and M Makara and S-J Hsu and P Buggisch and D Samuel and D Mutimer and B Nault and M Merz and W Bao and Griffel, {L H} and C Brass and Naoumov, {N V} and {ESSENTIAL II Study Group}",

note = "{\textcopyright} 2015 John Wiley & Sons Ltd.",

year = "2015",

month = oct,

doi = "10.1111/apt.13342",

language = "English",

volume = "42",

pages = "829--44",

journal = "Alimentary Pharmacology & Therapeutics",

issn = "0269-2813",

publisher = "Wiley",

number = "7",

}

Zeuzem, S, Flisiak, R, Vierling, JM, Mazur, W, Mazzella, G, Thongsawat, S, Abdurakhmanov, D, Van Kính, N, Calistru, P, Heo, J, Stanciu, C, Gould, M, Makara, M, Hsu, S-J, Buggisch, P, Samuel, D, Mutimer, D, Nault, B, Merz, M, Bao, W, Griffel, LH, Brass, C, Naoumov, NV & ESSENTIAL II Study Group 2015, 'Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)', Alimentary Pharmacology & Therapeutics, vol. 42, no. 7, pp. 829-44. https://doi.org/10.1111/apt.13342

TY - JOUR

T1 - Randomised clinical trial

T2 - alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

AU - Zeuzem, S

AU - Flisiak, R

AU - Vierling, J M

AU - Mazur, W

AU - Mazzella, G

AU - Thongsawat, S

AU - Abdurakhmanov, D

AU - Van Kính, N

AU - Calistru, P

AU - Heo, J

AU - Stanciu, C

AU - Gould, M

AU - Makara, M

AU - Hsu, S-J

AU - Buggisch, P

AU - Samuel, D

AU - Mutimer, D

AU - Nault, B

AU - Merz, M

AU - Bao, W

AU - Griffel, L H

AU - Brass, C

AU - Naoumov, N V

AU - ESSENTIAL II Study Group

PY - 2015/10

Y1 - 2015/10

N2 - BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance.AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection.METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.

AB - BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance.AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection.METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.

U2 - 10.1111/apt.13342

DO - 10.1111/apt.13342

M3 - Article

C2 - 26238707

SN - 0269-2813

VL - 42

SP - 829

EP - 844

JO - Alimentary Pharmacology & Therapeutics

JF - Alimentary Pharmacology & Therapeutics

IS - 7

ER -

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

Abstract

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