1Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre les Nancy, France. Electronic address: email@example.com.
2Groupe Hospitalier Pitié Salpêtrière, Université Pierre et Marie Curie, Paris, France.
3Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
4Mercy Medical Center, Baltimore, MD, USA.
5Hospital Provincial del Centenario, University of Rosario School of Medicine, Rosario, Argentina.
6The Research Institute, Springfield, MA, USA.
7Université Paris Descartes, INSERM U-1016, APHP, Hôpital Cochin, Paris, France.
8Universidad del Salvador Hospital de Gastroenterología Bonorino Udaondo, Buenos Aires, Argentina.
9Gastro One, Germantown, TN, USA.
10Bristol-Myers Squibb, Princeton, NJ, USA.
11Bristol-Myers Squibb, Wallingford, CT, USA.
BACKGROUND & AIMS:
Asunaprevir is a selective HCV NS3 protease inhibitor active against genotypes 1, 4, 5, and 6 in vitro. We evaluated asunaprevir plus peginterferon alfa-2a/ribavirin (pegIFNα/RBV) for genotype 1 and 4 chronic HCV.
In this phase 2b, double-blind, placebo-controlled study, treatment-naive adults with genotype 1 (n=213) or 4 (n=25) were randomly assigned (3:1) to asunaprevir 200 mg or placebo twice daily plus pegIFNα/RBV. Asunaprevir recipients achieving protocol-defined response (PDR; HCV-RNA below quantification limit at week 4 and undetectable at week 10) were rerandomized at week 12 to continue asunaprevir-based triple therapy or receive placebo plus pegIFNα/RBV for weeks 13-24. Patients without PDR and placebo recipients continued pegIFNα/RBV through week 48. Co-primary endpoints were undetectable HCV-RNA at weeks 4 and 12 (eRVR) and 24 weeks posttreatment (SVR24).
Most patients were male (64.3%), white (83.6%), and had non-CC IL28B genotypes (71.3%). Among genotype 1 patients, eRVR rates (asunaprevir vs placebo) were 67% (80% CI 62, 72) versus 6% (80% CI 2, 10); corresponding SVR24 rates were 64% (80% CI 59, 68) versus 44% (80% CI 36, 53). SVR24 among genotype 4 patients was 89% (asunaprevir) versus 43% (placebo). Rates of rash and hematologic adverse events were similar between treatment groups. Five asunaprevir-treated patients had grade 4 alanine aminotransferase elevations that resolved following discontinuation (n=4) or with continued dosing (n=1).
Addition of asunaprevir to pegIFNα/RBV in treatment-naive genotype 1- or 4-infected patients improves response rates and is well tolerated, with aminotransferase elevations that were manageable with appropriate monitoring.