• Hepatology

• Hepatology

Twelve weeks of treatment with the all-oral combination of daclatasvir (DCV), asunaprevir (ASV), and beclabuvir (BCV) resulted in sustained virologic response (SVR12) rates of > 92% in treatment-naïve patients with hepatitis C virus (HCV) genotype (GT) 1 and 100% in patients with HCV genotype 4 in phase 2 studies [Everson GT et al. AASLD. 2013 LB-1; Hassanein T et al. EASL. 2014]. The aim of the phase 3 UNITY-1 trial [NCT01979939], presented by Fred Poordad, MD, University of Texas Health Sciences Center, San Antonio, Texas, USA, was to evaluate this all-oral, ribavirin-free combination in noncirrhotic treatment-naïve and treatment-experienced patients with HCV GT 1 infection.

DCV is a pangenotypic (genotypes [GT] 1–6 in vitro and GT 1–4 in clinical trials) NS5A inhibitor with a low potential for drug-drug interactions. It is approved in Europe and Japan, and it is under regulatory review in the United States. ASV is an N53 protease inhibitor with clinical data available for GT 1 and 4. BCV is a nonnucleoside NS5B polymerase inhibitor with clinical data available for GT 1 and 4. DCV/ASV/ BCV is coformulated as a twice-daily, fixed-dose combination (FDC).

In the UNITY-1 trial, 312 treatment-naïve patients and 103 treatment-experienced patients were treated with DCV 30 mg/ASV 200 mg/BCV 75 mg FDC (DCV-TRIO) for 12 weeks and followed through week 48. The primary end point was SVR12, defined as HCV RNA < lower limit of quantitation (LLOQ) at posttreatment week 12, in treatment-naïve patients. The secondary end point was SVR12 in treatment-experienced patients.

All enrolled patients were aged ≥ 18 years, the median age was 55 years, and 58% were male. All patients had HCV RNA ≥ 10 000 IU/mL. Most of the patients (73%) were infected with HCV GT 1a. Most treatment-naïve and treatment-experienced patients had the non-CC IL28B GT. Treatment was completed by 97% of the patients. Eight patients discontinued due to lack of efficacy. Overall, SVR12 was achieved by 91% of the patients.

The SVR12 rate in treatment-naïve patients was 92%, significantly higher than the historic threshold rate of 79% (based on analysis of sofosbuvir plus peginterferon/ribavirin data). A significantly higher SVR12 rate of 89% was achieved in treatment-experienced patients, compared with the historic threshold rate of 48% (based on analysis of simeprevir plus peginterferon/ribavirin data).

SVR12 rates of 98% to 100% were observed in treatment-naïve and treatment-experienced patients with HCV GT 1b. SVR12 rates were comparable with respect to gender, age, race, baseline HCV RNA, and IL28B genotype. On-treatment virologic breakthrough occurred in 2% of both treatment-naïve and -experienced patients. Posttreatment relapse occurred in 5% and 15% of treatment-naïve and -experienced patients, respectively. The most frequently observed resistance-associated variants among GT 1a patients were NS5A-Q30, NS3-R155, and NS5B-P495.

Treatment with the all-oral, ribavirin-free, fixed-dose DCV-TRIO for 12 weeks achieved an SVR12 of 91% in noncirrhotic patients with HCV genotype 1. DCV-TRIO was generally safe and well tolerated.

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