PO-066 : A Long-Term, Observational, Follow-Up Study of Patients Treated in Phase 2 and 3 Clinical Studies with Daclatasvir- Based Regimens: Efficacy and Safety Outcomes

Background/aims: Daclatasvir plus other direct-acting antivirals (DAAs) and/or peg-interferon/ribavirin has achieved high rates of sustained virologic response (SVR) in multiple clinical studies of patients. This follow-up study evaluates the long-term efficacy and safety outcomes in these patients. Methods: : This 144-week observational study enrolled patients treated with ≥ 1 dose of daclatasvir within 6 months of either completing their parent studies or protocol availability at the study site. The study objectives were to evaluate SVR12 durability, persistence of emergent NS5A and NS3 substitutions in non-responders, and to characterize events of hepatic disease progression or hepatocellular carcinoma. Results: This study enrolled 1503 patients treated with DAA-only (n = 893) or interferon-containing (n = 610) regimens of daclatasvir, of whom 60% were male, 18% were aged ≥ 65 years, 87% had HCV genotype 1 infection, and 18% had cirrhosis. Overall, 1329/1489 evaluable patients archived SVR12 in parent studies; 1316 (99%) maintained SVR until their most recent follow-up visit. 12 responders relapsed after achieving SVR12 (9 on/before and 3 after post-treatment week 24); 1 was re-infected. Relapse occurred in 3/842 (0.4%) and 9/487 responders (2%) treated with DAA-only regimens and interferon-containing regimens, respectively. From parent study end of treatment, hepatic disease progression (n = 15) or new hepatocellular carcinoma (n = 23) were diagnosed in 36 patients (two had both); median time to diagnosis was 70 weeks (range, 0.4-206 weeks). These 36 patients were generally older (median, 61 years versus 56 years), more had cirrhosis at baseline (50% versus 18%), and most were infected with HCV genotype 1a (36%) or 1b (61%). Complete replacement of emergent NS5A, NS3 substitutions by wild-type sequences was observed in 27/157 (17%), 35/47 (74%) non-responders, respectively. Conclusions: The results suggest that SVR12 achieved with daclatasvir- based regimens is durable in the long term. Hepatic disease progression events and new hepatocellular carcinoma were infrequent.