Short-duration, IFN- RBV-free regimen for HCV 3
Posted on April 10, 2015
A short-duration, interferon- and ribavirin-free regimen of daclatasvir plus sofosbuvir is efficacious and tolerable in patients with chronic hepatitis C genotype 3 infection
Patients with chronic hepatitis C genotype 3 (HCV 3) infection have a higher risk of progression to cirrhosis, as well as development of steatosis or hepatocellular carcinoma, than those patients harboring other HCV genotypes. Patients with chronic HCV 3 infection are also in need of improved treatment options of short duration and without the addition of pegylated IFN (Peg-IFN) or ribavirin (RBV). An all-oral combination of sofosbuvir (SOF) plus RBV is US-approved for the treatment of HCV 3 infection, but this regimen requires 24 weeks of treatment because shorter treatment durations are associated with lower response rates. In addition, this 24-week regimen is associated with an increased incidence of anemia, which is consistent with the hemolytic anemia known to occur with RBV treatment. IFN- and RBV-free therapy options for both treatment-naïve and treatment-experienced patients with HCV 3 infection are currently limited.
Results of an open-label, phase 3 study of RBV-free treatment with daclatasvir (DCV) 60 mg plus SOF 400 mg once-daily for 12 weeks (with a subsequent 24-week follow-up) in treatment-naïve and treatment-experienced adult patients chronically infected with HCV 3 were recently published in a rapid communication in the journal Hepatology (Nelson DR et al. Hepatology. 2015;61:1127-1135). Patients with compensated cirrhosis as determined by liver biopsy were included in this trial (up to 50% in each patient cohort). A total of 152 patients received at least 1 dose of study medication and of these, 101 (66%) were treatment-naïve and 51 (34%) were treatment experienced. Patients were 90% white and 59% male, with a median age of 55 years.
- Coprimary endpoints: DCV plus SOF for 12 weeks achieved SVR12 rates of 90% in treatment naïve patients and 86% in treatment-experienced patients with HCV genotype 3 infection, with an overall SVR12 rate of 89%
- Rapid and sustained reductions from baseline in HCV-RNA levels were observed
- HCV-RNA levels were undetectable at end of treatment in ≥99% of patients
- Analysis of SVR12 in patient subgroups based on baseline characteristics showed no notable differences by gender, age, HCV-RNA levels, or IL28B genotype
- This study included patients who previously failed treatment with SOF- or alisporivir (ALV) containing regimens, of whom 71% and 100%, respectively, achieved SVR12
- SVR12 rates were higher in patients without cirrhosis (96%) than in patients with cirrhosis (63%), although high response rates at end of treatment were noted both in patients with and without cirrhosis (97% and 100%, respectively)
- The 63% SVR12 rate in patients with cirrhosis is comparable to that achieved with 16 (61%) or 24 weeks (67%) of SOF plus RBV, with the advantages of an IFN-free and shorter-duration regimen
- Occurrence of virologic failure was low, with no virological breakthroughs observed
- DCV plus SOF was well tolerated, with no AEs leading to discontinuation of treatment and few treatment-emergent grade 3/4 laboratory abnormalities
- There were no deaths and only 1 serious AE (SAE) was reported on-treatment: an event of gastrointestinal hemorrhage that was considered not related to study medications
- The most common AEs (in >10% of patients) were headache, fatigue, and nausea, and the incidence of grade 3 AEs was low (2%), with no grade 4 AEs reported
The authors conclude that DCV plus SOF, without the addition of RBV and with a shorter treatment duration relative to currently approved all oral regimens, demonstrated high SVR12 rates across patient subgroups, except in patients with cirrhosis and regardless of past treatment response. Additional evaluation to optimize efficacy in genotype 3-infected patients with cirrhosis is underway.