BOSTON, MA—Elbasvir/grazoprevir (EBR/GZR) and sofosbuvir (SOF) with and without ribavirin (RBV; EBR/GZR + SOF ± RBV) regimen was generally safe and effective for cirrhotic patients with hepatitis C virus (HCV) GT3 infections, according to an author of the UK-based randomized, open-label C-ISLE trial that were presented at The Liver Meeting® 2016.
“High efficacy was demonstrated in treatment-naive and treatment-experienced cirrhotic HCV GT3-infected patients,” said lead study author Graham R. Foster, MD, of Queen Mary University in London. “There were no virologic failures among patients receiving EBR/GZR+SOF ± RBV for 12 or 16 weeks.”
“Treatment duration longer than 12 weeks is not needed,” he said. The regimen exhibited high efficacy “regardless of baseline NS5A RAVs or patient characteristics.”
GT3 is a common genotype in hepatitis C virus, representing nearly a third (30%) of HCV infections around the world. It is associated with rapid progression to cirrhosis and high risk for developing hepatocellular carcinoma (HCC).
“Despite recent advances, HCV GT3 infections and cirrhosis are challenging to treat with all-oral regimens,” Dr. Foster said. “Treatment-experienced patients and those with baseline NS5A resistance-associated variants (RAVs) are particularly challenging.”
The C-SWIFT trial previously demonstrated that EBR/GZR+SOF ± RBV is associated with high rates of sustained virological resistance (SVR > 90%) for treatment-naïve GT3-infected patients, Dr. Foster said. “It had similar efficacy in cirrhotic patients treated for 12 weeks and non-cirrhotic patients treated for 8 to 12 weeks.”
Next, the study authors sought to evaluate longer EBR/GZR+SOF ± RBV regimen treatment durations of 8 to 16 weeks. The treatment durations of 8-16 weeks. Dosing was: EBR/GZR FDC (50mg/100mg per day), SOF (400 mg per day), and RBV (800-1400mg per day).
One hundred treatment-naïve adult patients with compensated cirrhosis and HCV GT3 infections were administered EBR/GZR + SOF with RBV for 8 weeks (n=23) or without RBV for 12 weeks (n=23); EBR/GZR + SOF for 12 (n=18) or 16 weeks (n=18); or EBR/GZR+SOF+RBV for 12 weeks (n=18). Sixty-eight percent of patients were male, 69% were white, 29% were Asian, and the average age was 53 years.
At 12 weeks, SVR ranged from 91% among patients in the 8-week EBR/GZR+SOR+RBV study group, to 100% in the 12-week EBR/GZR+SOF group. SVR12 was 94% for the 16-week group and the 12-week EBR/GZR+SOF+RBV group, and 96% for the 12-week EBR/GZR+SOF group.
Drug-related adverse events including fatigue, nausea, and skin rash/pruritus. Serious adverse events (SAEs) did not occur in the 8-week EBR/GZR+SOF+RBV group; in the other study groups, SAE rates were: 2.4% in the 12-week EBR/GZR+SOF group, 16.7% in the 12-week EBR/GZR+SOF+RBV group, and 5.6% in the 16-week EBR/GZR+SOF group.
Only two patients (both in the 8-week EBR/GZR+SOV+RBV group) relapsed. The 3 patients who failed to achieve SVR withdrew for “administrative reasons,” and not toxicities, Dr. Foster said. Two were treatment-experienced patients who discontinued after day 7, and a treatment-naïve participant was lost to followup.
NS5A resistance associated variants (RAVs) were present in 51% of patients.
Dr Foster’s financial disclosures included board membership at Boehinger Ingelheim, and advisory committees, review panels, speaking and teaching fees, as well as research grants, from several pharmaceutical companies, including BMS, Chughai, Gilead, GlaxoSmithKline, Idenix; Janssen, Merck, Novartis, Roche, and Tibotec.