Six weeks of Gilead Sciences’ triple regimen of a fixed-dose combination of Sovaldi (sofosbuvir) and GS-5816 plus GS-9857 cured a high rate of easier-to-treat people with genotype 1 of hepatitis C virus (HCV). It was less successful among those with cirrhosis and especially people who had failed a previous treatment. Researchers presented results from a Phase II study of the regimen, as well as pre-clinical studies of GS-9857’s antiviral activity against genotypes 1 through 6, at the 50th International Liver Congress in Vienna, Austria.

GS-5816 is an NS5A inhibitor and GS-9857 is an NS3/4A protease inhibitor.

Ninety-three percent (14 of 15) of the treatment-naive, non-cirrhotic participants achieved a sustained virologic response 12 weeks after completing therapy (SVR12, considered a cure). Eighty-seven percent (13 of 15) of treatment-naive, cirrhotic participants were cured, as were 67 percent (20 of 30) of those who had failed a previous cure attempt with two or more direct-acting antivirals.

The trial also gave the triple regimen to 15 genotype 1 participants for four weeks. Only four of them were cured, an SVR rate of 27 percent.

The regimen was generally well tolerated. The most frequent side effects were nausea (25 percent), headache (24 percent) and fatigue (16 percent). Four people (5 percent) experienced transient, asymptomatic, elevated lipase (grade 3 or 4), a digestive enzyme produced by the pancreas that aids in digesting dietary fat.

The pre-clinical research showed that GS-9857 is potent in fighting genotypes 1 through 6 of the virus and also is less likely to lead to viral resistance than other protease inhibitors. Researchers gave the drug for three days to people with genotypes 1 through 4 and found that the 100-milligram dose lowered viral loads by three powers of 10.

“These data support the ongoing development of GS-9857 and the potential for an all-oral, triple combination therapy containing Sovaldi, GS-5816 and GS-9857 to attempt to further reduce treatment duration for hepatitis C patients,” Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, said in a press release. “We are encouraged by the six-week SVR12 rates and other data presented at EASL demonstrating this regimen’s pan-genotypic potential, and have recently initiated additional Phase II studies to further evaluate the appropriate treatment duration of this regimen for all patients, regardless of genotype, including those who have failed prior therapy with directly acting antivirals and those with cirrhosis.”

To read the Gilead press release, click here.