SAN FRANCISCO – A simple, fixed-dose, one-pill combination of sofosbuvir and velpatasvir (SOF/VEL) was found superior to the current standard of sofosbuvir and ribavirin (SOF/R) for treatment of genotype 2 (GT2) hepatitis C virus (HCV) in a phase 3 multicenter, open-label trial presented at the annual meeting of the American Association for the Study of Liver Diseases.
There were no virologic failures on SOF/VEL, which produced a higher 12-week sustained virologic response (SVR12) rate than SOF/R (99% vs. 94%; P = .018) while avoiding ribavirin-related adverse events such as fatigue, reported Dr. Mark S. Sulkowski, medical director of the Viral Hepatitis Center at Johns Hopkins University, Baltimore.
“This combination is currently under regulatory review. If approved, SOF/VEL for 12 weeks will provide a single-tablet, once-daily, highly-effective, ribavirin-free regimen for treatment of patients with genotype 2 infection,” Dr. Sulkowski said.
In this study, which was published on the day of presentation (N Engl J Med. 2015 Nov 17. doi: 10.1056/NEJMoa1512612), 266 patients were randomized to SOF/VEL (400 mg SOF and 100 mg VEL) or to 400 mg SOF plus ribavirin. The primary endpoint was HCV RNA less than 15 IU/mL 12 weeks after the completion of treatment. About 14% of patients had cirrhosis at the time of enrollment and another 14% were treatment experienced, including those with previous exposure to SOF.
Both regimens achieved a SVR12 of 100% in patients who were treatment experienced. In those with cirrhosis, SVR12 rates were 100% for SOF/VEL but only 93% for SOF/R achieved SVR12. Indeed, there were no virologic failures at all in the SOF/VEL arm. The only patient not achieving SVR12 on SOF/VEL left the study after a single dose of therapy.
About 60% of patients had a resistance-associated variant to nonstructural protein 5A, which is the target of VEL, but as there were no virologic failures on SOF/VEL, the presence of resistance-associated variants did not compromise efficacy.
Serious adverse events were uncommon in both arms. Grade 3 or higher laboratory abnormalities (9% vs. 12%) were higher on SOF/R, a difference attributed to the greater reductions in hemoglobin associated with ribavirin. Several nuisance side effects for patients, particularly fatigue (15% vs. 36%) and headache (18% vs. 22%) were also less common on SOF/VEL.
“In general, the adverse event profile did lead to improved quality of life profile [for SOF/VEL] across the 12-week treatment period,” Dr. Sulkowski said.
Due to the adverse events associated with ribavirin, SOF/VEL would have already been attractive as a therapy if it had achieved comparable efficacy to SOF/R, but the near 100% rate of efficacy suggests that this will be a new standard of care when this fixed-dose combination becomes available. In a separate summary of highlights at the meeting, Dr. Norah Terrault, director of viral hepatitis research at the University of California, San Francisco, singled out the study, calling these response rates across different subgroups of GT2 patients “excellent.”
“This now gives us a ribavirin-free option for genotype 2 patients,” Dr. Terrault said.
Dr. Sulkowski reported financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Merck, and Gilead, which was the sponsor of this study.