EASL 2013 Abstract #1413: Simeprevir (TMC435) With Peginterferon/Ribavirin for Treatment of Chronic HCV Genotype-1 Infection in Treatment-Naïve Patients: Results From QUEST-2, a Phase III Trial

CARE Liver Disease Faculty Canadian Perspectives from EASL 2013

Abstract 1413: Simeprevir (TMC435) With Peginterferon/Ribavirin for Treatment of Chronic HCV Genotype-1 Infection in Treatment-Naïve Patients: Results From QUEST-2, a Phase III Trial

Background: Simeprevir is a potent, once-daily, oral, investigational HCV NS3/4A protease inhibitor. QUEST-2 (NCT01290679) is a Phase III, randomised, double-blind, placebo-controlled trial assessing the efficacy, safety and tolerability of simeprevir versus placebo as part of a regimen including peginterferon α-2a (pegIFNα-2a) or pegIFNα-2b/ribavirin (PR) in treatment-naïve patients chronically infected with genotype-1 HCV. Safety and SVR12 results from a primary (week 60) analysis are presented.

Methods: Patients (n = 391), randomised 2:1 and stratified by HCV genotype-1 subtype and host IL28B genotype, received simeprevir (150 mg QD) + PR or placebo + PR for 12 weeks, followed by PR alone. Total treatment duration was 24 or 48 weeks (simeprevir group) based on response-guided therapy (RGT) criteria (HCV RNA < 25 IU/mL week 4 and undetectable week 12) or 48 weeks (placebo group).

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Results: Simeprevir/PR was superior to placebo/PR; SVR12: 81 vs. 50%, respectively (p < .001). The majority (91%) of simeprevir-treated patients met RGT criteria and completed treatment at week 24. Overall, 79% of simeprevir and 13% of placebo-treated patients achieved RVR. Treatment with simeprevir/PR led to lower rates of on-treatment failure and relapse compared to placebo/PR (7 vs. 32% and 13 vs. 24%, respectively). The incidence of AEs was similar between groups, regardless of the pegIFN used. The most common AEs were fatigue, influenza-like illness, pruritus and headache. A slightly higher proportion of simeprevir patients experienced rash and photosensitivity, compared to placebo (27 vs. 20% and 4 vs. 1%, respectively). There was no difference in the proportion of patients experiencing anaemia.

Conclusions/Key Take Away: Simeprevir 150 mg QD was well tolerated, leading to a high SVR12 rate of 81% when administered with either pegIFNα-2a or pegIFNα-2b. The majority of patients (91%) receiving simeprevir was able to shorten therapy to 24 weeks.

Simeprevir is likely to be the first second-generation protease inhibitor to receive regulatory approval in Canada. The QUEST-2 trial confirms the efficacy of simeprevir, which has several advantages over currently available PIs including once daily dosing, minimal side effects, and a higher likelihood of early treatment success enabling shorter treatment duration.
— CARE Liver Disease Faculty