An all-oral, ribavirin-free, interferon-free combination of three direct-acting antiviral agents that had achieved sustained virologic response in 92% of patients with chronic HCV genotype 1 infection has demonstrated even greater response in patients with genotype 4 infection.
An all-oral, ribavirin-free, interferon-free combination of three direct-acting antiviral agents that had achieved sustained virologic response (SVR) in 92% of patients with chronic HCV genotype 1 infection has demonstrated even greater response in patients with genotype 4 infection.
Twelve weeks of treatment with a combination of daclatasvir (an NS5A inhibitor), asunaprevir (an NS3 inhibitor), and BMS-791325 (a non-nucleoside NS5B polymerase inhibitor) achieved SVR12 in all patients with observed post-treatment data, with no virologic failures.
“Within the first two weeks, 100% of patients dropped their viral load to undetectable levels with the approved assay. That effect continued through the entire study and the SVR rate was 100% on week 12 or post week12,” said Tarek Hassanein, MD, of the Southern California GI and Liver Centers in Coronado, CA, who presented study results at Digestive Disease Week 2014 in Chicago, IL.
These results broaden the powerful antiviral activity of this regimen to genotype 4 (GT4) patients, while maintaining the safety and tolerability documented previously in GT1 patients.
Previous standard treatment for GT4 patients had been pegylated interferon and ribavirin for 24-28 weeks which achieved SVR rates of 60-70%. But rates were even lower in real experience where adherence to interferon regimens is low, Hassanein said.
Treatment-naïve, hepatitis C virus (HCV) GT4-infected patients were randomly assigned (1:1) to receive a twice-daily regimen of daclatasvir (DCV) 30 mg, asunaprevir (ASV) 200 mg, and BMS-791325 75 mg or 150 mg for 12 weeks.
Patients were 62% male, 91% white, and non-cirrhotic. All patients completed 12 weeks of therapy. HCV RNA was undetectable in 21/21 (100%) patients at the end of treatment. SVR at post-treatment week 12 (SVR12) was achieved by 10/11 patients in the BMS-791325 75 mg group and 9/10 patients in the 150 mg group.
Adverse reactions were mild and centered on headache, insomnia, pain, and nausea. None led to discontinuation of participation, Hassanein said.
Genotype 4 HCV patients are heavily concentrated in Middle Eastern and African countries, but there are populations all over the world, including in some immigrant populations in the US.
A phase 3 trial with a twice-daily fixed-dose combination of the 3 direct-acting antivirals is ongoing. Hassanein said because the results were achieved so quickly after start of treatment and with such high success, the next steps may be to see whether they can get those results at a shorter duration of therapy or by eliminating one of the drugs in the combination. Further studies should also look at whether the combination can be used to help patients with cirrhosis, he said.