1Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX email@example.com.
2eStudySite, San Diego, CA.
3AbbVie Inc., North Chicago, IL.
4Kansas City Gastroenterology & Hepatology, Kansas City, MO.
5Clinical Research Centers of America, Murray, UT.
ABT-493 is a hepatitis C virus (HCV) non-structural (NS) protein 3/4A protease inhibitor, and ABT-530 is an HCV NS5A inhibitor. These direct-acting antivirals (DAAs) demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistance in vitro.
In this open-label dose-ranging trial, antiviral activity and safety were assessing during 3 days of monotherapy with ABT-493 or ABT-530 in treatment-naïve adults with HCV genotype 1 infection, with/without compensated cirrhosis. Presence of baseline resistance-associated variants (RAVs) and safety were also evaluated.
Mean maximal decreases from baseline in HCV RNA were approximately 4 log10 IU/mL for all ABT-493 doses ranging from 100 mg - 700 mg and doses ≥40 mg for ABT-530. There was no meaningful difference in viral load decline in patients with or without compensated cirrhosis. Twenty-four (50%) of the baseline samples from patients treated with ABT-493 had RAVs to NS3/4A protease inhibitors. Among 40 patients treated with ABT-530, 6 (15%) carried baseline RAVs to NS5A inhibitors. Viral load declines in patients with single baseline NS5A RAVs were similar to those in patients without them. One patient harbored baseline RAVs at 3 NS5A positions and appeared to have slightly less robust viral load decline on Day 3 of monotherapy. No serious or Grade 3 (severe) or higher adverse events and no clinically relevant laboratory abnormalities were observed with either compound.
ABT-493 and ABT-530 demonstrated potent antiviral activity and acceptable safety during 3-day monotherapy in patients with HCV genotype 1 infection with/without compensated cirrhosis. Based on these results, phase 2 studies assessing the combination of these next generation DAAs for the treatment of chronic HCV infection in patients with and without compensated cirrhosis have been initiated.