In the Journals

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.

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.