Glecaprevir/Pibrentasvir: High SVR Rates in HCV GT 2, 4, 5, 6 Without Cirrhosis
BOSTON, MA—Patients with chronic hepatitis C virus (HCV) genotypes (GT) 2, 4, 5, or 6 infection without cirrhosis had SVR12 rates of 97% after 8 weeks of treatment with co-formulated glecaprevir/pibrentasvir, investigators from the SURVEYOR-II, Part 4, concluded at The Liver Meeting® 2016.
"Baseline viral load, genotype/subtype, F0–F3 fibrosis stage, presence of baseline polymorphisms, and prior treatment experience with interferon (IFN) or sofosbuvir (SOF)-based regimens did not impact achievement of SVR12,” noted Tarek I. Hassanein, MD, of the Southern California GI and Liver Centers and Southern California Research Center, Coronado, CA, and colleagues.
HCV GTs 2, 4, 5, and 6 have diverse global distributions, together accounting for about 23% of all HCV infections worldwide.
In previous Phase 2 studies, SVR12 rates of 98% were achieved following treatment with glecaprevir/pibrentasvir for 8 weeks in patients with GT2-infection and 100% for those treated for 12 weeks in patients with GT4–6 infection.
Co-formulated glecaprevir (formerly ABT-493, an NS3/4A inhibitor developed by AbbVie and Enanta) and pibrentasvir (formerly ABT-530, an NS5A inhibitor) are pangenotypic direct-acting antivirals (DAAs) with a high barrier to resistance.
SURVEYOR-II, Part 4, is a Phase 2, open-label randomized, multicenter study in which treatment-naïve or treatment experienced patients with chronic HCV and GT2, 4, 5, or 6 infection without cirrhosis were enrolled into a single arm to receive 8-weeks of once-daily glecaprevir/pibrentasvir (300mg/120mg).
Treatment-experienced patients had received IFN or pegylated interferon (pegIFN) ± ribavirin (RBV), or SOF + RBV ± pegIFN therapy.
The primary endpoint was the percentage of patients with SVR12, defined as HCV RNA <25 IU/mL 12 weeks after the last dose of study drug. For patients with GT2 who were DAA-naïve, non-inferiority of rates of SVR12 was evaluated by comparing to a historical standard of care, a rate of 95% with 12 weeks of SOF + RBV, if the lower confidence bound of the 2-sided 95% confidence interval is >89%. The study also assessed safety.
Of 203 patients enrolled, 145 (71%) had GT2 infection; 46 (23%), GT4; 2 (1%), GT5; and 10 (5%), GT6 infection.
At baseline, 48% of patients were male, 76% were white, median age was 55 years (range 19–83), and median BMI was 26.8 kg/m2 (range 17.3–65.7). A total of 176 patients (87%) were HCV treatment-naïve; 21 (10%) had received IFN-based and 6 (3%), SOF-based therapy. The median HCV RNA was 6.45 log10IU/mL (range 0.75–7.62). The majority of patients, 170 (84%), had fibrosis scores of F0–1; 12 (6%) had F2; and 21 (10%), F3. A total of 19 patients (9%) had previously used proton pump inhibitors.
The SVR12 rate was 98% (142 of 145 patients) for GT2; 93% (43 of 46) for GT4; 100% (2 of 2) for GT5; and 90% (10 of 10) for GT6-infected patients. Among DAA-naïve patients with GT2 infection, 8 weeks of treatment with glecaprevir/pibrentasvir yielded an SVR12 rate of 99% (135 of 137 patients) that was non-inferior to the historical 95% SVR12 rate of 12 weeks of SOF/RBV.
No baseline polymorphisms were detected in 25% of those with GT2, 56% of GT4, 100% of GT5, and 33% of GT6. Of the 42% of patients with GT2 infection who had “M” at NS5A amino acid position 31 at baseline, 96% achieved SVR12.
Overall, two virologic failures occurred, both as relapses in GT2-infected patients with prior treatment experience.
The most common adverse events were fatigue (18%), headache (14%), and nausea (11%). No patient discontinued due to an adverse event. Serious adverse events were reported in two patients; one had urosepsis and a second patient had cholecystitis, with both assessed as unrelated to study drug. One patient (0.5%) had a bilirubin grade ≥3 (3–10XULN).