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Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection ( ESSENTIAL II )
Author(s) -
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.,
Bao W.,
Griffel L. H.,
Brass C.,
Naoumov N. V.
Publication year - 2015
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13342
Subject(s) - medicine , ribavirin , gastroenterology , adverse effect , placebo , regimen , clinical endpoint , sofosbuvir , hepatitis c virus , clinical trial , immunology , virus , pathology , alternative medicine
Summary 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 IL 28B ). Addition of ALV to PR improved virological response in a dose‐dependent fashion. Overall, sustained virological response ( SVR 12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR 12 (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.