Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection

Abstract

The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.

Required concentration index quantifies effective drug combinations against hepatitis C virus infection

“…Triple combination treatment with SOF, LDV and SMV was most effective against genotype 1 ( Fig.4C ), and least effective against genotype 2 ( Fig.4D ). SOF plus DCV and SMV ( Fig.4C ) was also significantly effective against genotype 1, consistent with the reported clinical efficacy of this triple combination (20, 21).…”

Required concentration index quantifies effective drug combinations against hepatitis C virus infection

“…Triple combination treatment with SOF, LDV and SMV was most effective against genotype 1 (Fig.4C①), and least effective against genotype 2 (Fig.4D⑥). SOF plus DCV and SMV (Fig.4C②) was also significantly effective against genotype 1, consistent with the reported clinical efficacy of this triple combination (21,22).…”

Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1–6 and compensated cirrhosis: The EXPEDITION-8 trial

“…In the C-SWIFT trial, 24 8 weeks of elbasvir/ grazoprevir plus sofosbuvir treatment resulted in an SVR12 rate of 81% (n/N = 17/21) in treatment-naïve genotype 1-infected patients with compensated cirrhosis. In the ACCORDION study, 25 8 weeks of simeprevir, daclatasvir, and sofosbuvir in a small number of treatment-naïve genotype 1-infected patients with compensated cirrhosis resulted in an SVR12 rate of 100% (n/N = 9/9). The study reported here, EXPEDITION-8, is the first phase III trial to demonstrate the efficacy of an 8-week DAA regimen across HCV genotypes 1-6 in treatment-naïve patients with compensated cirrhosis.…”