SAN FRANCISCO, CA—The combination of two next-generation direct-acting antiviral (DAA) agents, ABT-493 and ABT-530, was “well tolerated,” with all non-cirrhotic patients with hepatitis C virus (HCV) genotype 1 (GT1) infection who completed the 8-week treatment period achieving sustained virologic response at 12 weeks (SVR12), a study presented at The Liver Meeting 2015® has found.
Fred Poordad, MD, of the Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, and colleagues evaluated the efficacy and safety of ABT-493, an NS3/4A protease inhibitor, and ABT-530, an NS5A inhibitor, co-administered for 8 weeks in non-cirrhotic patients with HCV GT1 infection, in Part 2 of the SURVEYOR-I study, an open-label multicenter Phase 2b study.
“Eligible patients were treatment-naïve or pegylated interferon treatment-experienced, between 18–70 years of age, without cirrhosis and no indication of HIV or HBV co-infection,” the study authors noted.
The primary endpoint was percentage of patients who achieved SVR12; additional endpoints included SVR4 and occurrence of virologic failure.
Of the 34 patients enrolled in the study, 56% were male; 97%, white race; and median age 54 years (range, 28–67 years); 70% (n=24) were fibrosis stage F0–F1; 15% (n=5) were F2, and 15% (n=5), F3. Median baseline HCV RNA was 6.5 log10 IU/mL. A total of 85% of patients were treatment-naïve and 15% pegylated interferon plus ribavirin treatment-experienced.
The study results showed all 34 patients (100%) achieved SVR4 and 97% (33 patients) achieved SVR12; 1 patient discontinued at Week 4 due to abdominal carcinoma of unknown origin unrelated to study treatment.
“All patients achieved HCV RNA levels below the lower limit of quantitation (25 IU/mL) by Week 4, regardless of baseline viral load, baseline fibrosis stage, or prior treatment history,” Dr. Poordad reported. In addition, “all patients who completed 8 weeks of treatment achieved SVR12, regardless of presence of baseline NS3 and/or NS5A variants.”
At baseline, 23 patients had variants in NS3 or NS5A known to confer resistance to at least one protease or NS5A inhibitor, if not to the two study drugs. Of the 23 patients, 16 had variants in NS3 only, 3 in NS5A only, and 4 to both NS3 and NS5A.
A total of 21 patients (62%) experienced adverse events (AEs); most were primarily grade 1 and included fatigue (18%), diarrhea (9%), nausea (9%), cough (9%), and urinary tract infection (9%).
“No additional serious AEs or deaths were reported,” they noted, and “no Grade 3 or higher on-treatment emergent liver function test or other laboratory abnormalities were reported.”
The authors concluded that these results “demonstrate the high potency of this once-daily dual DAA regimen of ABT-493 and ABT-530 against HCV GT1 and holds promise for confirming an 8-week treatment duration for non-cirrhotic patients with GT1 infection.”