A single-tablet regimen of sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks is safe, well tolerated, and highly effective in patients with chronic hepatitis C virus (HCV) infection who had previously failed treatment with an NS5A inhibitor, according to a new study.
The combination led to a 97 percent rate of sustained virologic response 12 weeks after the end of treatment (SVR12) in an open-label substudy of the POLARIS-1 trial.
Previously, the phase 3 POLARIS-1 trial showed the effectiveness of the direct-acting antiviral (DAA) combination of sofosbuvir (an NS5B inhibitor), velpatasvir (an NS5A inhibitor), and voxilaprevir (an NS3/4A protease inhibitor) and served as the basis for U.S. and European approvals.
The researchers published the results on May 30, 2018, in The Lancet Gastroenterology & Hepatology.
These latest results “add to the confidence of the regimen by considerably increasing the number of patients treated with it. A salvage regimen for this population represents an important advance for patients with limited retreatment options,” said the researchers led by Marc Bourlière, MD of the Hospital Saint Joseph, Marseilles, France.
He noted that POLARIS-1 is the only phase 3 registration study dedicated to enrollment of patients who were previously treated with NS5A inhibitors, and there have been few data for retreatment of these patients.
The substudy included 147 patients who had initially received placebo in POLARIS-1. They received a combination tablet of sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) once daily for 12 weeks.
More than three-quarters (113 patients) had HCV genotype 1a, while 30 patients had genotype 1b and 2 patients had genotype 6. One-third of patients had compensated cirrhosis. About two-thirds (91 patients) had previously received the NS5A inhibitor ledipasvir, while 27 patients had received daclatasvir and 24 received ombitasvir.
Most patients (89 percent) had baseline NS5A or NS3 resistance-associated substitutions, which had no discernible impact on SVR rates. The combination regimen produced high SVR rates regardless of cirrhosis status or previous treatment regimen.
All 147 patients completed treatment, and 143 patients (97 percent) achieved SVR12. Four (3 percent) patients had virological relapse; all had HCV genotype 1a infection and one patient also had compensated cirrhosis.
The most common adverse events were fatigue (21 percent), headache (20 percent), diarrhea (19 percent), and nausea (14 percent). No deaths, treatment discontinuations, or treatment-related serious adverse events occurred.
In an accompanying editorial, Imam Waked, MD, from the National Liver Institute in Menoufiya, Egypt, wrote: “Since sofosbuvir-velpatasvir-voxilaprevir results in a very high SVR rate in patients who have not responded to all types of direct-acting antiviral therapy, regardless of genotype and of the presence of NS3 or NS5A resistance-associated substitutions, its use as a first-line treatment in untreated patients is appealing.”
He noted that the use of this combination as first-line therapy for 12 weeks still needs to be further evaluated.
This regimen is a treatment of choice for HCV patients when NS5A or NS3 DAA therapy fails. The combination is recommended in clinical practice guidelines from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America, and from the European Association for the Study of the Liver.