Hong Kong-based biotech Ascentage Pharma (HKG: 6855) presented the Phase I clinical study results of its novel inhibitor of apoptosis proteins (IAP) antagonist APG-1387 in chronic hepatitis B virus (cHBV) at the Liver Meeting 2022 of the American Association for the Study of Liver Diseases (AASLD). The presentation highlighted the drug’s potential in treating cHBV, a significant public health challenge.
APG-1387 Profile
APG-1387 is a bivalent IAP antagonist designed to enhance HBV-specific T cell reactions and induce apoptosis in hepatocytes expressing HBV antigen. Preclinical studies have shown that the drug has significant potential in suppressing and clearing HBV infections.
Clinical Study Results
The Phase I study, the first to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of APG-1387 in Chinese cHBV patients, enrolled 49 patients, including 33 males, with 29 HBeAg positive cases and a median age of 31 years. The results indicated that APG-1387 was safe and well-tolerated as a cHBV treatment. The drug demonstrated significant anti-HBV activity at doses of 12 mg and 30 mg, with a continuous antiviral effect observed even after drug withdrawal. Additionally, APG-1387 showed a synergistic effect when used in combination with nucleos(t)ide analog (NA) sequential therapy.
Mechanism of Action
After treatment with APG-1387, markers of apoptosis such as M30/M65 and cytokines like IL-12 and IFN-γ increased, suggesting that the drug has a dual mechanism of inducing apoptosis and immune regulation. This dual action underscores APG-1387’s potential as a functional cure for cHBV.
Future Development
The preliminary data support the development of APG-1387 in combination with other therapies as a functional cure for cHBV. A Phase II study (NCT04568265) combining APG-1387 with entecavir is currently underway, further exploring the drug’s potential in this indication.-Fineline Info & Tech
