On July 29, 2020, Ascletis' all-oral HCV treatment has been approved for marketing in China by National Medical Products Administration (NMPA). The Company’s all-oral HCV treatment (RDV/DNV Regimen) is Ravidasvir (Asclevir®) in combination with Danoprevir (Ganovo®).
Our second HCV drug candidate, ravidasvir, which we believe is a best-in-class, NS5A protein inhibitor with pan-genotypic anti-viral activity, has completed a phase II/III clinical trial. We expect to file an NDA for ravidasvir in the third quarter of 2018. Our RDV/DNV Regimen (ravidasvir in combination with Ganovo and ribavirin) is an all-oral, interferon-free HCV therapy and demonstrates a 99% cure rate (SVR12) and a superior safety profile with a short treatment duration of 12 weeks. The current primary regimen in China has a cure rate of approximately 60% (SVR24) with a treatment duration of 48 to 72 weeks. Our RDV/DNV Regimen displays a higher genetic barrier to resistance than the approved regimens, Daklinza/Sunvepra. In patients with baseline NS5A resistance mutations, our phase II/III clinical trial showed that our RDV/DNV Regimen demonstrates a cure rate of 100% (SVR12).
Current Therapies and Limitations
See “Ganovo® — Current Therapies and Limitations”
Advantages of Asclevir®
We believe that, based on our clinical trials, our RDV/DNV Regimen has the potential to address the limitations of the current primary regimen for HCV in the following aspects:
• Best-in-class NS5A inhibitor. Our RDV/DNV Regimen demonstrated a 99% cure rate (SVR12) in the phase II/III clinical trial in China with 309 HCV genotype 1 patients. Our RDV/DNV Regimen was substantially more efficacious than the current primary regimen (48- to 72-week treatment duration) in China. The following diagram sets forth the virological response (RVR4, RVR8, EOT and SVR12) from this clinical trial.
• Highly efficacious for patients infected by HCV with baseline NS5A resistance mutations. The RDV/DNV Regimen demonstrated a 100% cure rate (SVR12) for patients with baseline NS5A resistance mutations in our phase II/III clinical trial. Six patients in our phase II clinical trial (EVEREST) had baseline NS5A resistance mutations and 100% of these patients achieved SVR12. 19% of HCV patients in China carry baseline NS5A resistance mutations. Competitor products demonstrated a cure rate of 20% (SVR12) in treating patients infected by HCV genotype 1b with baseline NS5A resistance mutations. The following diagrams set forth the SVR12 of patients with baseline NS5A resistance mutations in our phase II/III clinical trial and phase II clinical trial (EVEREST).
• Efficacious for hard-to-cure genotypes. Phase III clinical trial of RDV/SOF Regimen demonstrated a 99% cure rate (SVR12) in genotype 1a patients and 97% cure rate (SVR12) in genotype 3 patients. The following diagram sets forth the SVR12 of patients infected with hard-to-cure HCV genotypes in a phase III clinical trial for RDV/SOF Regimen.
• Efficacious in cirrhotic patients. Phase III clinical trial of RDV/SOF Regimen demonstrated a 96% cure rate (SVR12) in cirrhotic patients. The following diagram sets forth the SVR12 for cirrhotic patients in a phase III clinical trial.
• Efficacious for HCV/HIV co-infected patients. Phase III clinical trial of RDV/SOF Regimen demonstrated a 97% cure rate (SVR12) in HCV/HIV co-infected patients. The following diagram sets forth the SVR12 for HCV/HIV co-infected patients in a phase III clinical trial.
• Pan-genotypic anti-viral activity against genotypes 1 to 6. In vitro studies have shown that ravidasvir has potent anti-viral activity against HCV genotypes 1 to 6. Two phase III clinical trials of RDV/SOF Regimen demonstrated an overall 97% cure rate (SVR12) in genotypes 1, 2, 3 and 6 and 95% cure rate (SVR12) in genotype 4. The following diagram sets forth the SVR12 for the HCV genotypes indicated below in phase III clinical trials.
• Shorter treatment duration. Our 12-week RDV/DNV Regimen is significantly shorter than the 48 to 72 week treatment duration of the current primary regimen. We believe that a shorter regimen will increase compliance to the treatment and improve patient tolerability.
• Superior safety and tolerability profile. Our phase II/III clinical trial have shown our RDV/DNV Regimen to be safe and well-tolerated. There were no treatment-related serious adverse events. Except for anemia and hyperuricemia, the occurrence of adverse event was similar between the RDV/DNV treatment group and placebo group. The higher occurrence rate of anemia in the RDV/DNV treatment group may be related to the use of ribavirin.