PHILADELPHIA, PA—The QUAD regimen—daclatasvir and asunaprevir plus peginterferon alfa-2a and ribavirin (DCV+ASV+pegIFN/RBV)—demonstrated high sustained virologic response rates of 93% at post-treatment Week 12 (SVR12) in genotype 1 (GT 1) and 100% in genotype 4 (GT 4) patients with hepatitis C virus who were prior null or partial responders to pegIFN/RBV, results of a Phase 3 open-label study reported at IDWeek 2014.
“These results support the investigation of DCV in all-oral combinations in multiple patient populations across genotypes,” concluded Donald M. Jensen, MD, of the Center for Liver Diseases at the University of Chicago Medicine, Chicago, IL, and colleagues on behalf of the HALLMARK-QUAD Study Team.
Compared with pegIFN/RBV alone, the QUAD regimen was generally well tolerated, with no additional safety concerns.
In the HALLMARK-QUAD study, 354 patients with GT 1 infection and 44 patients with GT 4 infection received DCV 60mg once daily plus ASV 100mg twice daily in combination with weekly pegIFN alfa-2a 180µg and weight-based RBV (1000mg or 2000mg daily) for 24 weeks. The primary efficacy end point was SVR12 in GT 1 patients.
Median patient age was 53 years; 69% were male, 76% were white, and 23% had cirrhosis. Of the patients, 67% were prior null responders and 33% had partial responses. Prior responses to pegIFN/RBV, cirrhosis status, gender, age, race, or IL28B genotype were not found to influence SVR12, Dr. Jensen reported.
Serious adverse events (AEs) were reported in 6% of patients, with 5% discontinuing treatment due to an AE. Most AEs were typically associated with pegIFN/RBV. At post-treatment Week 12, one patient died of pneumonia, which was not considered related to the study therapy.
The AEs that occurred in 20% or greater of patients included fatigue, headache, pruritus, asthenia, influenza-like illness, insomnia, and rash. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%) and ALT/AST elevations (3%/3%), Dr. Jensen noted. No clinically relevant differences were observed in the safety profile between patients with or without cirrhosis.