Study: 12 weeks therapy combination cures virtually all HCV patients

Eight weeks of therapy with a combination of sofosbuvir, velpatasvir and voxilaprevir does not appear to be as effective as 12 weeks of sofosbuvir plus velpatasvir in patients with chronic hepatitis C virus (HCV) infection, according to the results of two phase 3 randomized clinical trials.

Studies show that patients with chronic HCV infection have high rates of sustained virologic response (SVR) following 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. However, a shorter duration of therapy for HCV may help limit the decline in patient compliance with longer courses of therapy. Nonadherence has become the biggest risk factor for treatment failure.

Researchers led by Ira M. Jacobson, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, assessed the efficacy of eight weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir in comparison to standard 12 weeks of sofusbuvir-velpatasvir.

The researchers published their results online on April 5, 2017 in the journal Gastroenterology.

In a pair of phase 3, open-label trials, patients with HCV infection who had not previously been treated with a direct-acting antiviral (DAA) agent were randomly assigned to groups given sofosbuvir-velpatasvir-voxilaprevir for eight weeks or sofosbuvir-velpatasvir for 12 weeks.

One trial, POLARIS-2, enrolled 941 patients from 117 sites in the United States, Canada, the United Kingdom, France, Germany, Australia and New Zealand who were infected with all HCV genotypes with or without cirrhosis, except patients with HCV genotype 3 and cirrhosis, who are more difficult to treat. This trial was designed to test the non-inferiority of eight weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir.

The other trial, POLARIS-3, enrolled 219 patients infected with HCV genotype 3 who had cirrhosis. It compared rates of SVR in both DAA combination treatments.

Next: The results

In the POLARIS-2 trial, 95% of the 501 patients on the triple combination of sofosbuvir-velpatasvir-voxilaprevir achieved an SVR after eight weeks. The doublet treatment of sofosbuvir-velpatasvir led to an SVR in 98% of 440 patients. Therefore, “the results did not meet the criterion to establish non-inferiority to 12 weeks of sofosbuvir-velpatasvir,” Jacobson told Medical Economics.

The difference in the efficacy, he said, was primarily due to a lower rate of SVR among patients with HCV genotype 1a infection receiving eight weeks of sofosbuvir-velpatasvir-voxilaprevir, who only achieved a 92% SVR.

In the POLARIS-3 trial, 96% of patients achieved an SVR in both treatment groups. This was significantly superior to the performance goal.

The most common adverse events in both trials were headache, fatigue, diarrhea and nausea, the researchers noted. Diarrhea and nausea were reported more frequently by patients receiving voxilaprevir.

In both trials, the proportions of patients who discontinued treatment due to adverse events were low (0–1%).

The researchers concluded that “in phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for eight weeks was non-inferior to sofosbuvir-velpatasvir for 12 weeks, but the two regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis.”