Jia-Horng Kao1, Min-Lung Yu2, Chi-Yi Chen3, Cheng-Yuan Peng4, Ming-Yao Chen5, Huoling Tang6, Qiaoqiao Chen6, Jinzi J Wu6. 1. Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan. 2. Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 3. Division of Gastroenterology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan. 4. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. 5. Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan. 6. Ascletis BioScience Co., Ltd., Hangzhou, China.
Abstract
BACKGROUND AND AIM: The need for all-oral hepatitis C virus (HCV) treatments with higher response rates, improved tolerability, and lower pill burden compared with interferon-inclusive regimen has led to the development of new direct-acting antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis. METHODS: A total of 38 treatment-naïve, non-cirrhotic adult HCV GT1 patients were enrolled in this multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight < 75/≥ 75 kg) for 12 weeks. The primary endpoint was the rate of sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: Of 38 patients, all (100%) achieved SVR12. During the study, no treatment-related serious adverse events, no patients discontinued treatment due to adverse events, and no deaths were reported. Six of 37 (16%) patients with available sequences had HCV NS5A resistance-associated variants at baseline. All patients (6/6) with baseline NS5A resistance-associated variants achieved SVR12. CONCLUSIONS: Twelve-week RDV and DNVr in combination with RBV for 12 weeks achieves the SVR12 rate of 100% in treatment-naïve non-cirrhotic Asian patients with HCV GT1 infection. This interferon-free regimen is also safe and well tolerated.
BACKGROUND AND AIM: The need for all-oral hepatitis C virus (HCV) treatments with higher response rates, improved tolerability, and lower pill burden compared with interferon-inclusive regimen has led to the development of new direct-acting antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis. METHODS: A total of 38 treatment-naïve, non-cirrhotic adult HCV GT1 patients were enrolled in this multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight < 75/≥ 75 kg) for 12 weeks. The primary endpoint was the rate of sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: Of 38 patients, all (100%) achieved SVR12. During the study, no treatment-related serious adverse events, no patients discontinued treatment due to adverse events, and no deaths were reported. Six of 37 (16%) patients with available sequences had HCV NS5A resistance-associated variants at baseline. All patients (6/6) with baseline NS5A resistance-associated variants achieved SVR12. CONCLUSIONS: Twelve-week RDV and DNVr in combination with RBV for 12 weeks achieves the SVR12 rate of 100% in treatment-naïve non-cirrhotic Asian patients with HCV GT1 infection. This interferon-free regimen is also safe and well tolerated.