POLARIS-2: Voxilaprevir safe, effective with Epclusa in multiple HCV genotypes
BOSTON — A novel pangenotypic protease inhibitor, voxilaprevir, yielded encouraging outcomes when administered with Epclusa, regardless of HCV genotype or cirrhosis status, but remained non-inferior to the combination direct-acting antiviral, according to findings presented at The Liver Meeting 2016.
“Sof/vel/vox for 8 weeks resulted in a 95% SVR rate in DAA-naive genotype 1 to 6 patients with or without cirrhosis,” Ira M. Jacobson, MD, chair of the department of medicine at Mount Sinai Beth Israel Medical Center and co-Chief Medical Editor for HCV Next, said during his presentation. “The regimen did not meet noninferiority as compared to the 98% SVR12 rate with sof/vel for 12 weeks and the difference between the regimens was largely attributed to more relapses amongst patients with genotype 1a infection in the sof/vel/vox group.”
Jacobson presented phase 3 findings for voxilaprevir (Gilead Sciences) 400 mg in a fixed-dose combination with Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) for 8 weeks as compared with 12 weeks of sofosbuvir/velpatasvir alone. Researchers stratified participants with HCV genotypes 1 through 6 (n = 941) by genotype, treatment history with interferon and cirrhosis status.
Baseline data indicated that 23% of the cohort had failed previous interferon therapy, and 32% had the IL28B CC genotype. SVR12 with a non-inferiority margin of 5% served as the primary endpoint. Nearly 20% of included patients had cirrhosis, but genotype 3 patients with cirrhosis were enrolled in a separate study.
Jacobson and colleagues randomly assigned 501 participants to 8 weeks of the triple therapy (sof/vel/vox) and 440 to 12 weeks of sofosbuvir/velpatasvir (sof/vel).
“This study was regarded as an opportunity to study less common genotypes with the newer regimen, sof/vel/vox, so the intent was to assign genotypes 5 and 7 to that group,” Jacobson said.
Nearly every patient completed the drug therapy with only four discontinuations
Results indicated that 95% of patients reached SVR in the study regimen and 98% for sofosbuvir/velpatasvir. There were no virologic breakthroughs among patients on treatment.
“This study actually failed to demonstrate non-inferiority based on this data,” Jacobson said. “The reason for this was shown by the difference in virologic failures: 4.2% in the sof/vel/vox and 0.7% in the sof/vel group. More specifically, you can see the substantial difference in the rate of relapse with many few relapsers seen in the sof/vel group.”
For genotype 1 patients, Jacobson showed 93% SVR rates in the triple regimen and 98% for the sofosbuvir/velpatasvir group.
“This is driven essentially entirely in the difference in the genotype 1a patients,” Jacobson said, showing 92% SVR with 14 relapses vs. 99% SVR with one relapse for triple vs. double therapy, respectively, in genotype 1a.
In the other genotypes, results were more similar, all triple vs. double unless otherwise noted:
- Genotype 2: 97% vs. 100%;
- Genotype 3: 99% vs. 97%;
- Genotype 4: 92% (two relapsed, three lost to follow-up) vs. 98%;
- Genotype 5: 94% with triple therapy only; and
- Genotype 6: 100% vs. 100%.
When stratifying by cirrhosis status, Jacobson showed that in those without cirrhosis, triple therapy produced a 96% SVR rate with 14 relapses, compared with 98% in the sofosbuvir/velpatasvir group, which had just two relapses. In those with cirrhosis, he showed that the triple therapy produced a 91% SVR rate with seven relapses while sofosbuvir/velpatasvir produced a 99% SVR rate with just one relapse.
“Both regimens were safe and well tolerated,” Jacobson said.
While no serious treatment-related adverse events were reported, diarrhea and nausea were more common with the study regimen. There were no deaths in the study.
“This very large study demonstrates the value of large, controlled trials to compare highly effective regimens to try to glean differences between them,” Jacobson said. – Katrina Altersitz and Rob Volansky
Jacobson IM, et al. Abstract LB-12. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.
Disclosures: This study was funded by Gilead Sciences. Jacobson reports consulting for AbbVie, Achillion, Bristol-Myers Squibb, Gilead, Intercept, Janssen, Merck and Trek; receiving grant or research support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck; and speaking and teaching for AbbVie, Bristol-Myers Squibb, Gilead and Janssen.