BOSTON, MA—The all-oral, ribavirin-free glecaprevir/pibrentasvir regimen achieved high SVR12 rates in non-cirrhotic patients with hepatitis C virus (HCV) genotype (GT) 4, 5, and 6 infection, the Phase 3 ENDURANCE-4 study concluded at The Liver Meeting® 2016.
These results were observed regardless of prior treatment experience or fibrosis status, said Tarik Asselah, MD, PhD, Centre de Recherche sur l’Inflammation, Clichy, France.
The ongoing multicenter, open label, single arm study is being conducted to confirm the results of the Phase 2b SURVEYOR-1 study, which yielded 100% SVR12 rates in 34 patients with GT 4, 5, or 6 infection without cirrhosis following treatment with glecaprevir (formerly ABT-493), a NS3/4A protease inhibitor, and pibrentasvir (formerly ABT-530), a NS5A inhibitor.
Both agents, pangenotypic protease inhibitors, demonstrate a high barrier to resistance, potent activity against common NS3A and NS5A variants, and additive/synergistic antiviral activity, Dr. Asselah said.
Specifically, the study is investigating the safety and efficacy of 12 weeks of treatment with once-daily co-formulated glecaprevir/pibrentasvir in adults with chronic HCV GT 4, 5, or 6 infection without cirrhosis who were either HCV treatment-naïve or treatment-experienced: interferon or pegylated interferon ± ribavirin, or sofosbuvir plus ribavirin ± pegylated interferon.
Patients were excluded if they had cirrhosis, as determined by a liver biopsy (METAVIR score ≤3), a FibroScan score <12.5 kPa, or a FibroTest score of ≤0.48 and an APRI <1. Also excluded were those co-infected with hepatitis B or HIV, creatinine clearance <50mL/min, or other causes of liver disease.
The primary endpoint was number and percentage of patients achieving SVR12. Adverse events, on-treatment virologic failure, and post-treatment relapse were additional endpoints.
ENDURANCE-4 enrolled 121 patients at 32 sites across 8 countries in Europe, North America, and Africa. Median age was 54 years (range 20–80), 64% were male, and median BMI was 24.8 (range 18.5–43.6).
A total of 76 patients (63%) were infected with GT4, 26 (21%) with GT5, and 19 (16%) with GT6. At baseline, mean HCV RNA was 6.13 log10IU/mL (range 3.6–7.3); 39 patients (13%) were treatment-experienced; 14% had fibrosis stage F2–F3; and 75% had non-CC IL28B genotype.
Results showed that 120 of the 121 patients (99%) without cirrhosis achieved SVR12 in the intent-to-treat population, and there were no virologic failures, Dr. Asselah said.
By genotype, SVR12 rates were 99% for GT3, 100% for GT5, and 100% for GT6. One patient in the GT4 patient discontinued treatment on day 12 due to a transient ischemic attack (TIA).
In the modified intent-to-treat population, the SVR12 rate was 100%.
The glecaprevir/pibrentasvir regimen was well tolerated. The most commonly occurring adverse events (AEs) were headache in 25 patients (21%) and fatigue in 21 (17%). One patient (0.8%) had a serious adverse event, the TIA; a second TIA occurred 24 days following discontinuation and the patient had not yet returned for the SVR12 visit.
Three patients (2%) had AEs that led to study drug discontinuation; these presented with anxiety, heartburn, and TIA.
An estimated 26 million people worldwide are infected with HCV GT4, 5, and 6, accounting for approximately 15% of global infections.