SAN FRANCISCO, CA—According to data from a proof-of-concept study, once-daily oral combination of daclatasvir (DCV) + sofosbuvir (SOF) with or without ribavirin (RBV) achieved a sustained virologic response in chronic HCV GT1 infected patients with prior telaprevir (TVR) or boceprevir (BOC) + peginterferon/ribavirin treatment failures, as presented at IDWeek 2013. Daclatasvir is a first in class NS5A replication complex inhibitor.

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The current standard of care for chronic HCV genotype (GT) 1 infection is telaprevir or boceprevir + peginterferon/ribavirin. Patients with IL28B CT or TT genotypes, prior null response to pegIFN-alfa/RBV, or <1 log decline in HCV RNA after 4-week pegIFN-alfa/RBV therapy have high rates of virologic failure during or after standard of care therapy.

In a Phase 2, randomized, open-label, parallel-group study, Mark Sulkowski, MD, from John Hopkins University School of Medicine, Baltimore, MD, and colleagues assessed the safety and efficacy of DCV + SOF with or without RBV for 24 weeks in a total of 41 genotype (GT) 1 non-cirrhotic patients with previous breakthrough (n=15), relapse (n=13), or non-response (n=14) to peginterferon/ribavirin + telaprevir (n=33) or boceprevir (n=9).

Patients were randomized 1:1 to DCV 60mg daily + SOF 400mg daily with or without RBV (500–600mg twice daily) for 24 weeks. Most patients had HCV GT1a (83%), were IL28B non-CC (98%), and had estimated METAVIR stage ≥F2 (83%). Patients who discontinued TVR or BOC due to adverse events were excluded. The primary efficacy endpoint was HCV RNA <25 IU/mL at 12 weeks post-treatment (SVR12).

At Week 4, HCV RNA <25 IU/mL was achieved in 21/21 (100%) of the DCV + SOF group and in 19/20 (95%) of the DCV + SOF + RBV group. All patients achieved HCV RNA <25 IU/mL by the end of treatment.  No patients experienced breakthrough or relapse, and all patients with available data achieved SVR12.

Overall, SVR12 was achieved in 98% of non-cirrhotic GT1 patients with prior TVR or BOC with the once-daily DCV + SOF combination with or without RBV for 24 weeks.

Adverse events occurring in ≥10% of patients in this study were fatigue, headache, alopecia, arthralgia, constipation, and diarrhea. All events were mild or moderate (Grade 1/2).

Dr. Sulkowski stated, “The combination of two potent direct-acting antivirals with different viral targets is effective in patients who failed peginterferon/RBV and a protease inhibitor.”  Currently multiple Phase 2 and 3 trials assessing the efficacy and safety of different daclatasvir-based regimens are ongoing.