On June 8, 2018, the NDA approval for danoprevir was granted by the NMPA and we have begun to commercialize GANOVO®(danoprevir) in China.
GANOVO® is an NS3/4A protease inhibitor, which, when administered in combination with pegylated interferon and ribavirin (Ganovo Regimen), demonstrates a 97% cure rate (SVR12) and superior safety profile with a short treatment duration of 12 weeks.
Advantages of GANOVO®
We believe that Ganovo Regimen has the following advantages:
• Higher cure rate. Ganovo Regimen demonstrated a 97% cure rate (SVR12) in a phase III clinical trial completed on 140 HCV patients. The following diagram sets forth the virologic response (including RVR4, RVR8, EOT and SVR12) from our phase III clinical trial.
• Superior safety and tolerability profile. No grade 3 or higher laboratory liver function abnormalties were observed in our phase III clinical trial of the Ganovo Regimen. Moreover, there was no discontinuation of use due to adverse events. The rate of serious adverse events potentially related to the use of Ganovo Regimen was approximately 0.7%.
• Potent anti-viral activity. GANOVO® demonstrated potent activity against HCV NS3/4A protease derived from HCV genotypes 1 through 6 with sub-nanomolar to nanomolar potencies. In clinical trials, our Ganovo Regimen has shown an overall cure rate over 97% (SVR12) against HCV genotype 1 and 4 infections.
•Efficacy in cirrhotic patients. Clinical trials have demonstrated that Ganovo Regimen had a 91% cure rate (SVR12) in cirrhotic patients in Taiwan.
• High genetic barrier to resistance. No pre-treatment genetic resistance testing is required for GANOVO®based on clinical trial results and expert consensus due to its high genetic barrier to resistance. In the phase III clinical trial, no virological breakthrough (on-treatment failure) occurred in patients receiving treatment.
On July 29, 2020, Ascletis' all-oral HCV therapy has been approved for marketing in China by National Medical Products Administration (NMPA). The Company’s all-oral HCV therapy (RDV/DNV Regimen) is Ravidasvir (ASCLEVIR®) in combination with Danoprevir (GANOVO®).
Our second marketed HCV drug , ASCLEVIR® is a best-in-class, NS5A inhibitor with pan-genotypic anti-viral activity, has completed a phase II/III clinical trial. RDV/DNV Regimen (ravidasvir in combination with danoprevir and ribavirin) is an all-oral, interferon-free HCV therapy ，demonstrates a 99% cure rate (SVR12) and a superior safety profile with a short treatment duration of 12 weeks. RDV/DNV Regimen displays a higher genetic barrier to resistance than the approved regimens, Daklinza/Sunvepra. The Phase II/III clincal trial showed RDV/DNV Regimen demomstrated a cure rate of 100% (SVR12) for the patients with baseline NS5A resistance-associated substitutions (RASs).
Advantages of ASCLEVIR®
According to the results of the clincal trials，The RDV/DNV Regimen has the potential to address the limitations of the current primary therapy for CHC with following aspects：
• Best-in-class NS5A inhibitor. RDV/DNV Regimen demonstrated a 99% cure rate (SVR12) in the phase II/III clinical trial in China with 309 HCV genotype 1 patients. 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-associated substitutions（RASs）. The RDV/DNV Regimen demonstrated a 100% cure rate (SVR12) for patients with baseline NS5A RASs in the Phase II/III clinical trial. Six patients in Phase II clinical trial (EVEREST) with baseline NS5A RASs and 100% of these patients achieved SVR12. 19% of HCV patients in China with baseline NS5A RASs. Competitor products demonstrated a cure rate of 20% (SVR12) in treating patients infected by HCV genotype 1b with baseline NS5A RASs. The following diagrams set forth the SVR12 of patients with baseline NS5A RASs in Phase II/III clinical trial and Phase II clinical trial (EVEREST) of RDV/DNV Regimen.
• Efficacious for hard-to-cure genotypes. Phase II/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 II/III clinical trial for RDV/SOF Regimen abroad.
• Efficacious in CHC patients with cirrhotic. Phase II/III clinical trial of RDV/SOF Regimen abroad，demonstrated a 96% cure rate (SVR12) in CHC patients with cirrhotic . The following diagram sets forth the SVR12 for these patients in phase II/III clinical trial abroad.
• Efficacious for HCV/HIV co-infected patients. Phase II/III clinical trial of RDV/SOF Regimen abroad，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 II/III clinical trial abroad.
• Pan-genotypic anti-viral activity against genotypes 1 to 6. Ravidasvir showed the potent anti-viral activity against HCV genotopyes 1-6 in vitro. Two phase II/III clinical trials of RDV/SOF Regimen abroad， 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 these two phase II/III clinical trials.
• Superior safety and tolerability profile. Phase II/III clinical trial have shown the 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 ribavirin.
Pegasys® is licensed from Shanghai Roche Pharmaceuticals Ltd. for the exclusive rights in the Mainland China.