8-week sofosbuvir-velpatasvir-voxilaprevir less effective for HCV

Last Updated: 2017-04-24

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - For patients with chronic hepatitis C virus (HCV) infection, eight weeks of combined sofosbuvir-velpatasvir-voxilaprevir may not be as effective as 12 weeks of only sofosbuvir-velpatasvir, results from two phase 3 open-label trials suggest.

But patients with HCV genotype 3 and cirrhosis may have similar rates of sustained virologic response (SVR) to either treatment, researchers report in Gastroenterology, online April 5.

"Among patients who have not been treated with direct-acting antiviral agents (DAAs), the triple regimen of the DAAs sofosbuvir/velpatasvir/voxilaprevir for eight weeks achieved very high rates of efficacy, curing 95% of patients with chronic HCV infection; however, it failed to achieve noninferiority against the 12-week regimen of sofosbuvir/velpatasvir, which cured 98% of patients," said lead author Dr. Ira M. Jacobson of the Icahn School of Medicine at Mount Sinai, in New York City.

"Therefore, an 8-week regimen of the three-drug combination cannot be recommended as an equally effective alternative for all patients," he told Reuters Health by email.

In each of the two studies, POLARIS-2 and POLARIS-3, Dr. Jacobson and his colleagues randomly assigned patients with HCV infection who had not previously been treated with a DAA to receive either the three-drug combination for eight weeks or the two-drug combination for 12 weeks.

In POLARIS-2, the team enrolled 941 participants at 117 sites in the United States, Canada, the United Kingdom, France, Germany, Australia and New Zealand. Patients infected with any of the HCV genotypes, with or without cirrhosis, were included, except those with genotype 3 and cirrhosis. In POLARIS-3, they enrolled 219 participants infected with HCV genotype 3 and compensated cirrhosis who were excluded from POLARIS-2.

In POLARIS-2, 95% of the 501 participants on triple therapy for eight weeks showed SVR, which did not meet the non-inferiority criterion compared with the 98% SVR seen in the 440 participants on the 12-week dual therapy.

The difference in efficacy was mainly due to a lower rate of SVR (92%) among participants with HCV genotype 1a infection who were on the three drugs for 8 weeks. In POLARIS-3, 96% of both treatment groups showed SVR.

In both studies, the most common adverse events reported were headache, fatigue, diarrhea and nausea, with diarrhea and nausea more frequent in patients on voxilaprevir; in both trials, only between 0% and 1% of participants discontinued treatment due to adverse events.

"There is a universal desire to shorten the duration of therapy for hepatitis C to maximize patient compliance, which may decline in the process of a longer course of therapy," Dr. Jacobson noted.

As Dr. Jacobson and his co-authors write, for HCV-infected people who are homeless, incarcerated, or have addictions, access to highly effective treatment can be challenging; and overall, nonadherence has become the biggest risk factor for treatment failure.

But, he added, "The already-approved 12-week regimen of sofosbuvir/velpatasvir, along with other already-approved regimens, appears unlikely to be routinely replaced by a shorter duration of the triple regimen for patients who have not been treated with direct-acting antiviral agents.”

Co-author Dr. Brian L. Pearlman of the Medical College of Georgia in Augusta, said, "DAAs have been a major advance relative to the difficult-to-tolerate interferon-containing therapies of the past. It was presumed that adding medications with multiple mechanisms of action would further engender improvements in efficacy rates and/or durations of therapy."

"One of the few remaining 'difficult-to-treat' chronic hepatitis C patients is the genotype 3-infected cirrhotic. The triple-combination antiviral therapy studied in POLARIS-3 will likely represent a new, effective 8-week treatment option for this patient group, even in those who have failed prior therapies," Dr. Pearlman, also at Emory University School of Medicine in Atlanta, told Reuters Health by email.

Gilead Sciences supported the study. Most of the authors, including Drs. Jacobson and Pearlman, have financial relationships with the company, and several are employees.

SOURCE: http://bit.ly/2pcX9bq

Gastroenterology 2017.