DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha‐2a/ribavirin in HCV genotypes 1 or 4

Abstract

The combination of danoprevir/r plus P/R is efficacious in treatment-naïve patients with HCV genotype 1 or 4 infection.

Ritonavir-boosted danoprevir-based regimens in treatment-naive and prior null responders with HCV genotype 1 or 4 and compensated cirrhosis

“…As reported previously in noncirrhotic patients, the nature and incidence of AEs of danoprevir/r-based triple therapy was typical of that associated with peginterferon/ribavirin [10,13]. The low incidence of Grade 3 or 4 laboratory abnormalities is also consistent with previous studies of triple therapy in noncirrhotic patients [10,13]. The safety profile of the quadruple therapy regimen in cirrhotic null responders was similar to that previously reported in non-cirrhotic null responders [13].…”

“…No patients experienced Grade 4 anemia or Grade 4 ALT elevations, and no patients experienced hepatic decompensation in this trial. As reported previously in noncirrhotic patients, the nature and incidence of AEs of danoprevir/r-based triple therapy was typical of that associated with peginterferon/ribavirin [10,13]. The low incidence of Grade 3 or 4 laboratory abnormalities is also consistent with previous studies of triple therapy in noncirrhotic patients [10,13].…”

“…The SVR24 rate (39 %) in treatment-naive patients was considerably lower than that reported in non-cirrhotic patients receiving the same treatment regimen in the DAUPHINE study (79 %) [10], which highlights the challenge of achieving viral clearance in patients with advanced liver disease. The subset analyses by viral and host genotype demonstrate that these factors influence the ability to achieve SVR24 in the same way that they do in non-cirrhotic patients when treated with a triple regimen for 24 weeks: higher SVR24 rates were observed in patients with HCV G1b infection (89 vs. 8 % in G1a) and in patients with an IL28B CC genotype (50 vs. 35 % with non-CC).…”

“…Danoprevir is administered with the pharmacokinetic booster ritonavir (danoprevir/r) because ritonavir inhibits the metabolism and maintains therapeutic trough levels of danoprevir, as evidenced by the reported potent short-term antiviral activity and long-term efficacy demonstrated in HCV-infected patients [10,12]. This permits less frequent administration of lower doses of danoprevir without compromising antiviral activity [10,[13][14][15].…”

“…Danoprevir is a potent macrocyclic inhibitor of the HCV NS3/4A serine protease [9][10][11][12][13][14]. Danoprevir is administered with the pharmacokinetic booster ritonavir (danoprevir/r) because ritonavir inhibits the metabolism and maintains therapeutic trough levels of danoprevir, as evidenced by the reported potent short-term antiviral activity and long-term efficacy demonstrated in HCV-infected patients [10,12].…”