Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis

TLDR

High rates of sustained virologic response were achieved with 12‑week ledipasvir‑sofosbuvir therapy in HCV patients. This phase‑3 open‑label study evaluated whether 8‑week ledipasvir‑sofosbuvir, with or without ribavirin, is non‑inferior to 12‑week therapy in treatment‑naïve genotype 1 HCV patients without cirrhosis. Patients (n = 647) were randomized to 8‑week ledipasvir‑sofosbuvir, 8‑week ledipasvir‑sofosbuvir plus ribavirin, or 12‑week ledipasvir‑sofosbuvir, and sustained virologic response at 12 weeks post‑treatment was the primary endpoint. The 8‑week ledipasvir‑sofosbuvir regimen achieved a 94 % SVR12 rate, non‑inferior to the 95 % rate with 12 weeks and 93 % with ribavirin, with no added benefit from ribavirin or extended duration, and ribavirin increased adverse events. Funded by Gilead Sciences; ION‑3 ClinicalTrials.gov NCT01851330.

Abstract

High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy.The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events.Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330.).