All‐oral 12‐week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY‐3 phase III study

Abstract

Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection are limited, with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3; http://ClinicalTrials.gov: NCT02032901) evaluated the 12-week regimen of daclatasvir (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF; pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were either treatment naïve (n = 101) or treatment experienced (n = 51) and received DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving a sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12 rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naïve and treatment-experienced patients, respectively; no virological breakthrough was observed, and ≥99% of patients had a virological response (VR) at the end of treatment. SVR12 rates were higher in patients without cirrhosis (96%; 105 of 109) than in those with cirrhosis (63%; 20 of 32). Five of seven patients who previously failed treatment with an SOF-containing regimen and 2 of 2 who previously failed treatment with an alisporivir-containing regimen achieved SVR12. Baseline characteristics, including gender, age, HCV-RNA levels, and interleukin-28B genotype, did not impact virological outcome. DCV plus SOF was well tolerated; there were no adverse events (AEs) leading to discontinuation and only 1 serious AE on-treatment, which was unrelated to study medications. The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient. Conclusion: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of patients with genotype 3 infection without cirrhosis and was well tolerated. Additional evaluation to optimize efficacy in genotype 3–infected patients with cirrhosis is underway. (Hepatology 2015;61:1127–1135)

Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme

“…Thirty‐seven patients with cirrhosis (compensated and decompensated) were treated for 10‐14 weeks, most (89% [33/37]) without RBV, and their 70% SVR12 (mITT) rate was consistent with the 63% ITT rate in patients with compensated cirrhosis after 12 weeks of DCV+SOF in ALLY‐3 8. This suggests that RBV may be required for shorter (<24 week) treatment of genotype 3 infection with cirrhosis.…”

“…The majority (62% [48/77]) of non‐cirrhotic patients had advanced (F3) fibrosis, and their 96% SVR12 rate (mITT) after 12 or 24 weeks of DCV+SOF±RBV is similar to non‐cirrhotic patients treated with DCV+SOF for 12 weeks in ALLY‐3 (ITT 96%) and patients with F3 fibrosis treated for 12 or 16 weeks with DCV+SOF+RBV in ALLY‐3+ (ITT 100%) 8, 12. Although real‐world and clinical study findings must be compared with caution, these data suggest that DCV+SOF without RBV for 12 weeks is effective in non‐cirrhotic genotype 3 infection, including patients with advanced fibrosis.…”

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

“…The recommendation for use of DCV/SOF in HCV GT-3 is based on the ALLY-3 study, 57 which included treatmentnaive (n = 101) and treatment-experienced (n = 51) patients, who were treated with DCV/SOF therapy for 12 weeks. SVR12 rates were 90% (91 of 101) and 86% (44 of 51) in treatment-nǎive and treatment-experienced patients, respectively.…”

Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis

“…Experience of different DAA combinations in the real world is growing within a number of compassionate use programs [5,7]. However, virological response with all oral DAAs in decompensated cirrhosis, particularly in HCV genotype 3, is lower than in patients with less advanced liver disease [8,9]. Remaining uncertainties in treating such patients include the optimal duration of therapy, whether or not the regimen should include ribavirin, and what, if any, clinical benefits accrue to patients with such advanced liver disease following clearance of virus.…”