Vosevi effective rescue therapy in patients with chronic HCV after DAA treatment failure

WASHINGTON — Vosevi, a triple-combination therapy for chronic hepatitis C virus infection, was effective when used as a rescue treatment in patients who did not achieve sustained virologic response with direct-acting antiviral agents.

“Despite a high efficacy in overall safety of the DAAs, still about 2% of patients fail to achieve SVR,” Christiana Graf, MD, of Goethe University Hospital in Frankfurt, Germany, told attendees at The Liver Meeting. “Those patients need an alternative treatment option, and according to the international guidelines for AASLD as well as EASL, the combination of [voxilaprevir/velpatasvir/sofosbuvir (vox/vel/sof)] is recommended as the standard treatment regimen in those DAA failures.”

Graf and colleagues conducted a retrospective, longitudinal, multicenter study and enrolled 458 adult patients with HCV from 2015 to 2020 who were treated with Vosevi (voxilaprevir/velpatasvir/sofosbuvir, Gilead Sciences) for 12 weeks after DAA failure.

Graf presented results from 433 patients with complete follow-up data, noting “a relatively high proportion of our study cohort carried at least one difficult-to-treat cofactor,” which included liver cirrhosis (39%), previous hepatocellular carcinoma (9%), HCV genotype 1a (51%) and genotype 3 (40%), Epclusa (velpatasvir/sofosbuvir, Gilead Sciences) pretreatment (17%) and resistance-associated substitutions (RAS, 83%).

According to results, 94% of patients achieved SVR by per-protocol analysis.

“Significantly lower SVR rates could be observed in patients with previous HCC history, patients with liver cirrhosis, among patients with liver cirrhosis and high Child-Pugh score, and in patients that have been liver transplanted,” Graf said. “In contrast, treatment effectiveness was not affected by the genotype, by baseline HCV RNA, by use of ribavirin and by presence of baseline RAS.”

Although previous velpatasvir/sofosbuvir experience, HCC history, liver cirrhosis, LT and elevated Child-Pugh score affected SVR rates, “liver cirrhosis and HCC history turned out to be the only independent and predictive factors of a treatment failure for vox/vel/sof” after consecutive multivariate analysis, Graf noted.

“In contrast, RAS did not impact the SVR,” she said. “We also observed excellent SVR rates in patients with rare genotypes and chimera.”

She added, “We can conclude that we have certain, excellent overall effectiveness of vox/vel/sof in patients with prior DAA failure included in a real-life setting.”