BOSTON, MA—Treatment with single tablet sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks “is a highly effective salvage therapy” for patients who did not previously achieve sustained virologic response (SVR) following treatment with non-NS5A inhibitor-containing direct-acting antivirals (DAAs), results from the POLARIS-4 study presented at The Liver Meeting® 2016 have shown.
Patients who do not achieve SVR with DAA-based regimens represent an unmet medical need, said Stefan Zeuzem, MD, Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany, and colleagues.
The investigators conducted an open-label, randomized, active-comparator Phase 3 study to evaluate SOF/VEL/VOX compared to SOF/VEL in DAA-experienced patients with hepatitis C virus (HCV) infection with genotypes 1-6 who had not previously received an NS5A inhibitor. The contribution of the components of the three-drug regimen was also explored.
The study enrolled 333 patients at 102 sites in the United States, Canada, France, Germany, the United Kingdom, Australia, and New Zealand. Those with genotypes 1, 2, or 3 at screening were randomly assigned 1:1 to receive SOF/VEL/VOX or SOF/VEL for 12 weeks (n=182), while those of all other genotypes were assigned to receive SOF/VEL/VOX for 12 weeks (n=151). All patients were stratified according to genotype and cirrhosis status.
Excluded were DAA-experienced patients previously treated with an NS5A inhibitor or with an NS3/4A protease inhibitor in combination with ribavirin and pegylated-interferon.
The primary endpoint evaluated the superiority of SVR12 of each treatment to a prespecified performance goal of 85%.
In the SOF/VEL/VOX arm, mean age was 57 years (range 25-85) and 79% were male. A total of 18% of patients had the IL28B CC genotype, 46% had compensated cirrhosis, and 43% had genotype 1 HCV infection.
These baseline demographics were similar in the SOV/VEL arm. Mean age was 57 years (range 24-80) and 75% were male. The IL28B CC genotype was present in 19%; 46% had compensated cirrhosis, and 43% had genotype 1 HCV infection.
Most patients had prior DAA experience with either an NS5B inhibitor alone (73%) or an N5SB inhibitor and an NS3/4A protease inhibitor (25%).
After 12 weeks of treatment, 177 of 182 patients (97%) in the SOF/VEL/VOX arm achieved SVR12 (P<0.001), as did 136 of 151 (90%) in the SOF/VEL arm (P=0.092). The SVR12 rates for those without cirrhosis were 98% for SOF/VEL/VOX and 94% for SOF/VEL; for those with cirrhosis, these rates were 96% and 86%, respectively.
In the SOV/VEL/VOX arm, SVR12 rates were 98% for GT1a, 96% for GT1b, 100% for GT2, 94% for GT3, and 100% for GT4. For the SOV/VEL arm, these rates were 89%, 95%, 97%, 85%, and 0%, respectively.
In the SOF/VEL/VOX arm, there was one relapse and one death, and one patient was lost to follow-up. In the SOF/VEL arm, there was one breakthrough and 14 patients relapsed.
Of the 22 patients with NS5B resistance-associated variants (RAVs), all achieved SVR12. No treatment-resistant RAVs were observed in the one patient who relapsed after treatment with SOV/VEL/VOX; however, in the SOV/VEL arm, 10 of the 15 patients with virologic failure developed Y93H or Y93C.
In the SOV/VEL/VOX arm, all patients completed the study and none discontinued; in the SOF/VEL arm, two patients discontinued, one due to an adverse event (headache at Day 56) and one due to lack of efficacy.
Treatment was well tolerated. The most commonly reported adverse events (AEs) were headache, fatigue, diarrhea, and nausea. No serious AEs attributed to either study medication were reported. The four serious AEs in the SOF/VEL/VOX arm were abdominal hernia, congestive cardiac failure, intervertebral disc protrusion, and a fatal illicit drug overdose. In the SOF/VEL arm, the 4 serious AEs were unstable angina, cerebrovascular accident, lumbar spine stenosis, and road traffic accident.