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Resistance analysis of Epclusa shows patients may retreat with sofosbuvir

Treatment with Epclusa for 12 weeks resulted in high sustained virologic response rates among patients with hepatitis C genotypes 1 through 6, irrespective of baseline NS5A resistance-associated substitutions, according to recently published data.

The researchers detected NS5A inhibitor resistance, but not resistance to sofosbuvir, in the few patients who did not achieve SVR.

“Treatment with [Epclusa] for 12 weeks was effective across highly diverse HCV subtypes,” Christophe Hézode, MD, PhD, from the Université Paris-Est, France, and colleagues wrote. “Most of the few patients who experienced virologic failure after treatment with [Epclusa] for 12 weeks had single class resistance to NS5A inhibitor velpatasvir, but not to the NS5B inhibitor sofosbuvir allowing for a possible retreatment with sofosbuvir-containing regimens.”

The researchers conducted resistance analyses of six phase 3 clinical trials of Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) for 12 weeks in a total of 1,778 patients with chronic HCV genotypes 1 through 6. Trials included the ASTRAL 1, 2, 3 and 5 studies and POLARIS-2 and POLARIS-3 studies.

The overall SVR across the studies was 98.9%. The SVR rates by genotype were 99% for genotype 1, 100% for genotype 2, 97.5% for genotype 3, 99.5% for genotype 4, and 100% for genotypes 5 and 6.

The overall prevalence of NS5A RASs was 28% in patients with available NS5A sequencing data (n = 1773). The lowest prevalence was 9% in patients with genotype 5 and the highest prevalence was 61% among patients with genotype 2.

Among patients with genotypes 1a, 1b, 2, 4, 5 or 6, the presence of NS5A RASs at baseline had no impact on SVR rate.

Twelve percent of patients with genotype 3 had NS5A RASs at baseline. Compared with those without NS5A RASs at baseline, patients with genotype 3 and NS5A RASs had a lower SVR rate at 12 weeks (93% vs. 98%).

Prevalence of baseline NS5A velpatasvir-specific RASs among the whole cohort was 8% (n = 138) with the lowest prevalence in patients with genotype 5 (0%) and the highest prevalence among patients with genotype 6 (52%).

“The lower prevalence of NS5A velpatasvir-specific RAS compared to NS5A class RASs is due to the improved resistance barrier of velpatasvir,” according to the researchers. The SVR rates for patients with genotypes 1 through 6 and velpatasvir-specific RASs ranged from 93% to 100% compared with 98% to 100% in patients without velpatasvir-specific RASs.

Twenty of the 1,778 patients treated with sofosbuvir/velpatasvir for 12 weeks did not achieve SVR. Of those, seven had HCV genotype 1, 12 had genotype 3, and one had genotype 4. – by Talitha Bennett

Disclosure: Hézode reports he served as a clinical investigator and speaker or consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme and Roche. Please see the full study for the other researchers’ relevant financial disclosures.