Date: 2015-11-16
Type of information: Presentation of results at a congress
phase: 3b
Announcement: presentation of results at the annual meeting of The American Association for the Study of Liver Diseases (AASLD), in San Francisco,
Company: BMS (USA - NY)
Product: Daklinza® (daclatasvir), sofosbuvir and ribavirin
Action
mechanism: direct-acting antiviral agent/nucleotide analog/RNA polymerase (NS5B) inhibitor/RNA polymerase (NS5A) inhibitor. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication. Daclatasvir is a NS5A replication complex inhibitor. Daklinza® is contraindicated in combination with medicinal products that strongly induce CYP3A and P-glycoprotein transporter, as this may lead to lower exposure and loss of efficacy of Daklinza®. Daklinza® must not be administered as a monotherapy.
Disease: genotype 3 hepatitis C (HCV) patients with advanced fibrosis or cirrhosis
Therapeutic area: Infectious diseases
Country:
Trial
details: ALLY-3+ study is an open-label, Phase 3b study in HCV genotype 3-infected treatment-naive or -experienced patients with advanced fibrosis or compensated cirrhosis randomized patients 1:1 to receive 12 weeks versus 16 weeks of Daklinza® (60 mg QD) + SOF (400 mg QD) + RBV (weight-based), stratified by advanced fibrosis or cirrhosis status. Fifty patients were treated (12 weeks: 24 patients; 16 weeks: 26 patients). The majority of patients were male (80%), white (98%), and treatment-experienced (74%; 10% prior relapse on SOF+RBV); 72% had cirrhosis and 52% had HCV RNA ?6 million IU/mL. Baseline characteristics were comparable between arms. The primary endpoint was to estimate SVR12 in treatment-naive or -experienced subjects with compensated advanced fibrosis/cirrhosis (F3-F4) treated for 12 weeks and for 16 weeks.
Latest
news: * On November 16, 2015, BMS announced late-breaking data from the Phase 3 ALLY-3+ trial investigating a regimen of Daklinza® (daclatasvir, DCV) in combination with sofosbuvir (SOF) and ribavirin (RBV) in genotype 3 hepatitis C (HCV) patients with advanced fibrosis or cirrhosis, for treatment durations of 12 and 16 weeks. This patient population is one of the most difficult to treat, among whom sustained virologic response (SVR) rates, or cure, have proved harder to achieve. The results show that 100% of patients in the advanced fibrosis (F3) cohort achieved SVR12 in both the 12- and 16-week arms of the study. SVR12 rates were 83% and 89% in patients with cirrhosis in the 12- and 16-week arms, respectively. Results have been presented at The Liver Meeting® 2015, the annual meeting of The American Association for the Study of Liver Diseases (AASLD), in San Francisco, CA, November 13 – 17. Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza® in combination with sofosbuvir for 12 weeks. In the ALLY-3+ study, the daclatasvir+sofosbuvir+ribavirin combination regimen had no discontinuations due to adverse events (AEs) or treatment-related serious AEs. The most frequent AEs were insomnia (30%), fatigue (26%) and headache (24%). Additionally, relapse occurred in four patients (two in the 16-week and two in the 12-week arm). There was one death (12-week arm; not treatment-related). There were no virologic breakthroughs.
