LBPE15 - Poster Exhibition
Ledipasvir/sofosbuvir is safe and effective as a single-tablet-regimen for treatment of patients with genotype 1 chronic hepatitis C virus, including those with compensated cirrhosis
M.S. Sulkowski1, K. Kowdley2, P. Ruane3, T. Hawkins4, R. Elion5, K. Workowski6, A. Mills7, M. Subramanian8, X. Ding8, S. Seyedkazemi8, R.H. Hyland8, J.C. Yang8, P.S. Pang8, J.G. Mchutchison8, N. Afdhal9, D. Wyles10
1Johns Hopkins University School of Medicine, Baltimore, United States, 2Virginia Mason Medical Center, Seattle, United States, 3Peter J. Ruane, MD, Inc, Los Angeles, United States, 4Southwest Care Center, Santa Fe, United States, 5Whitman Walker Clin., Washington, United States, 6Emory University School of Medicine, Atlanta, United States, 7Anthony Mills MD, Inc., Los Angeles, United States, 8Gilead Sciences, Inc., Foster City, United States, 9Harvard University School of Medicine, Beth Israel Deaconess Medical Center, Boston, United States, 10University of California San Diego, La Jolla, United States
Background: Simple, safe and effective treatment of genotype 1 (GT 1) chronic hepatitis C virus (HCV), without the use of pegylated-interferon (PegIFN) and ribavirin (RBV), remains an unmet medical need. The once-daily single-tablet-regimen of Ledipasvir (LDV), an NS5A inhibitor, and sofosbuvir, an NS5B nucleotide polymerase inhibitor, resulted in high rates of sustained virologic response (SVR) in phase 2 studies.
Methods: Three open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF administered with or without (±) RBV for treatment of GT 1 chronic HCV. There was no upper limit to age or body mass index (BMI). Treatment-naïve patients, including those with compensated cirrhosis, were randomized to 12 and 24 weeks of LDV/SOF ± RBV in the ION-1 study, while patients without cirrhosis were randomized to 8 weeks of LDV/SOF ± RBV or 12 weeks of LDV/SOF in the ION-3 study. HCV treatment-experienced patients, including those with compensated cirrhosis and prior HCV protease-inhibitor (PI) failure, were randomized to 12 and 24 weeks of LDV/SOF ± RBV in the ION-2 study. The primary endpoint was SVR at 12 weeks after the end of therapy (SVR12).
Results: Of the 1952 patients randomized and treated in these three phase 3 studies, 308 (16%) were African American, 224 (12%) had compensated cirrhosis, 591 (26%) had a BMI ≥ 30 kg/m2, 1597 (82%) had a high HCV viral load ≥ 800,000 IU/mL, and 440 (23%) were treatment-experienced. Of these 440 treatment-experienced subjects, 231 (53%) were prior HCV protease-inhibitor (PI) + PegIFN + RBV treatment failures. Overall, 97% of all patients achieved SVR12. The intent-to-treat SVR12 rates in all treatment arms are show in Figure 1. The most common adverse events (AEs) included fatigue, headache, nausea, and insomnia. Majority of AEs occurred more frequently in the RBV-containing arms of the studies.
Conclusions: A single-tablet-regimen of LDV/SOF, given once-daily, was highly effective in patients with genotype 1 HCV infection, including those with compensated cirrhosis and those who had previously failed triple therapy with a PI + PegIFN + RBV. The addition of RBV did not increase SVR rates but lead to higher rates of AEs.
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