LONDON — Previously untreated patients with HCV genotype 1 infection without cirrhosis who received treatment with a fixed-dose combination of sofosbuvir and ledipasvir for 8 weeks achieved sustained virologic response rates higher than 90%, according to new data from the ION-3 study.
At The International Liver Congress 2014, Kris V. Kowdley, MD, from Virginia Mason Medical Center in Seattle, said ION-3 is an open-label, phase 3 study assessing 8 and 12 weeks of therapy with sofosbuvir (Sovaldi, Gilead) and ledipasvir (Gilead) with or without ribavirin in treatment-naive, noncirrhotic patients with chronic HCV genotype 1 infection.
“There continues to be a need for treatments with a shorter duration of therapy,” Kowdley said at the meeting. “The aim of this study was to determine whether the addition of ribavirin to this combination or a longer duration of 12 weeks is necessary to achieve high SVR rates.”
The analysis included 647 patients who were randomly assigned in a 1:1:1 ratio to a fixed-dose combination of sofosbuvir 400 mg plus ledipasvir 90 mg for 8 weeks (n=215), combination therapy plus ribavirin for 8 weeks (n=216) or combination therapy without ribavirin for 12 weeks (n=216). Study groups were balanced with regard to baseline characteristics, according to Kowdley. “A substantial minority were black [6%] and Hispanic [19%],” he said.
Sustained virologic response at 12 weeks (SVR12) served as the primary outcome measure.
The SVR12 rate was 94% (95% CI, 90-97) with 8-week sofosbuvir/ledipasvir without ribavirin, 93% (95% CI, 89-96) with 8-week sofosbuvir/ledipasvir with ribavirin and 95% (95% CI, 92-98) with 12-week sofosbuvir/ledipasvir without ribavirin, according to Kowdley.
“These differences were not statistically significantly different from each other,” Kowdley said. “Breakthrough accounted for no cases of virologic failure. There was no relapse or loss to follow-up.”
In addition, host and viral factors traditionally associated with lower SVR rates did not affect SVR12 rates in this cohort, he said.
Compared with the rate of SVR in the group that received 8 weeks of sofosbuvir/ledipasvir, the SVR rate in the group that received 12 weeks of combination therapy was 1 percentage point higher and the rate in the group that received 8 weeks of sofosbuvir and ledipasvir was 1 percentage point lower, according to data published in The New England Journal of Medicine. The researchers said these results indicate noninferiority of the 8-week sofosbuvir/ledipasvir regimen.
Higher adverse event rates were reported for the ribavirin-containing regimen, according to Kowdley. However, there were no significant differences across the three groups with regard to grade 3 or 4 adverse events, which occurred in 3% to 8% of patients in the three cohorts. The adverse events that were reported in more than 5% in any arm included fatigue, headache, nausea, insomnia and irritability.
“These events were higher in the ribavirin group than in the non-ribavirin group,” Kowdley said. “Ribavirin contributed primarily to higher incidence of adverse events and laboratory abnormalities.”
The researchers concluded that either 8 or 12 weeks of this regimen with or without ribavirin is safe and effective for HCV genotype 1 disease. – by Rob Volansky
For more information:
Kowdley KV. Abstract #056. Presented at: The International Liver Congress 2014; April 9-13, 2014; London.
Kowdley KV. N Engl J Med. 2014;doi:10.1056/NEJMoa1402355.
Disclosure: Kowdley reports associations with companies including AbbVie, Boehringer Ingelheim, Gilead and Ikaria.