As a second generation of DAAs, velpatasvir (VEL) has demonstrated high SVR rates in patients with genotypes 1-6 HCV when used in combination with sofosbuvir (SOF). So could fixed dose combination of SOF/VEX be used effectively and safely in HCV infected patients with decompensated liver disease?
Michael Charlton, MD, Intermountain Medical Center, Salt Lake City, USA, reported the outcomes of “Sofosbuvir/velpatasvir for the treatment of HCV decompensated liver disease patients: ASTRAL-4 study”.
The researchers randomized GT1-6 HCV infected patients with CPT-B cirrhosis 1:1:1 to receive SOF/VEL (400 mg/100 mg) daily for 12 weeks, SOF/VEL + weight-based ribavirin (RBV) (1000 or 1200 mg/day) for 12-weeks, or SOF/VEL for 24 weeks. Patients with prior liver transplant or hepatocellular carcinoma were excluded.
The trials was done in a US population with 267 patients treated, most were male (70%), white (90%) and treatment experienced (55%). Patients had genotypes 1(78%), 2 (4.5%), 3 (15%), 4 (3%) or 6 (<1%) HCV infection. Although SOF/VEL + RBV for 12 weeks resulted in high SVR rates (95.6% compared with 83.3% and 85.6% of other groups), there was 1 (1%) GT1 and 2 (15.2%) GT3 subjects who experienced virologic failure and 1 GT3 patient who had virologic breakthrough.
Among patients who achieved SVR, 47% and 56% had improvements in CPT and MELD scores respectively at 12-week follow-up. Fatigue, headache and nausea were the most common adverse events.
Nine patients in total discontinued SOF/VEL due to adverse events. 18% (47) patients experienced serious adverse events and there were 9 deaths; but none were attributed to the study drug.
In conclusion, SOF/VEL + RBV for 12 weeks resulted in high SVR rates across all HCV genotypes in decompensated patients with early improvements in liver function. This regimen was well tolerated with AEs consistent with clinical sequelae of advanced liver disease and side effect profiles of RBV, according to Dr. Charlton.
This clinical trial was funded by Gilead Sciences.