Sofosbuvir-Velpatasvir-Voxilaprevir Effective in Previously Treated Chronic Hep C

By Will Boggs MD

June 13, 2018

NEW YORK (Reuters Health) - Sofosbuvir-velpatasvir-voxilaprevir is effective as salvage treatment for patients with chronic hepatitis C previously treated with an NS5A inhibitor, according to results of an open-label substudy of the POLARIS-1 trial.

The phase 3 POLARIS-1 study demonstrated the effectiveness of this combination and served as the basis for U.S. and European approvals.

Dr. Marc Bourliere from Hopital Saint Joseph, in Marseilles, France, and colleagues now report the safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir in 147 patients who received placebo in the primary study and were eligible for participation in the open-label substudy.

All but four patients (97%) achieved the primary efficacy outcome of sustained virological response at post-treatment week 12 (SVR12), and all 147 patients had HCV RNA concentrations below the lower limit of quantitation at the final treatment visit.

SVR12 rates were 97% (127/131) among patients with baseline resistance-associated substitutions and 100% among patients without resistance-associated substitutions or whose baseline resistance-associated substitutions could not be determined, the researchers report in The Lancet Gastroenterology & Hepatology, online May 30.

Common adverse events included fatigue, headache, diarrhea and nausea, but there were no serious adverse events deemed related to study treatment, and no patient discontinued treatment as a result of adverse events.

"A salvage regimen for this population represents an important advance for individual patients and public health initiatives," the researchers conclude.

Dr. Imam Waked from the National Liver Institute, in Menoufiya, Egypt, who wrote an accompanying editorial, told Reuters Health by email, "Patients who fail initial treatment can be retreated very effectively in almost all cases."

"The high response rates would encourage use as first line," he said. "However, the initial trial using it as first line used sofosbuvir-velpatasvir-voxilaprevir for 8 weeks compared to sofosbuvir-velpatasvir for 12 weeks, and the result was not 'non-inferior.' It was not tried for 12 weeks as initial therapy."

In his editorial, Dr. Waked notes, "The results presented in this article raise an important issue of whether this treatment will be available for the patients who need it most. 75% of patients with HCV infection live in low-income or middle-income countries (LMICs), where the number of patients treated annually has reached more than double the number of patients treated in high-income countries. Almost all therapy in LMICs is based on a combination of sofosbuvir plus an NS5A inhibitor, and patients who do not respond to therapy will need access to sofosbuvir-velpatasvir-voxilaprevir at reduced prices, similar to the access programs of the first-generation direct-acting antivirals."

Dr. Bourliere did not respond to a request for comments.

Gilead Sciences funded the study, employed several of the authors and had various relationships with the rest as well as with Dr. Waked.


Lancet Gastroenterol Hepatol 2018.