Conclusions
CHB
ADVERSE REACTIONS, VIRUS, CHB
Canocapavir was well tolerated. Most of the adverse reactions were grade I or II in severity. No dose-dependency was observed for either the frequency or intensity of AEs. Corresponding to 50–200-mg doses of Canocapavir, a linear PK profile and a low-to-mild accumulation rate (1.26–1.99) were notable. After oral dosing, significant margins were observed between plasma exposure of Canocapavir and its anti-HBV activity in vitro, supporting a once-a-day dosing in future trials. Canocapavir treatment for 28 days induced a substantial reduction of serum levels of both HBV DNA and HBV pgRNA in HBV patients. One subject (E2003) in the 50 mg of Canocapavir group did not respond to the treatment; this patient had a pre-existing mutation in the HBc (substitution of P25S), which is known to reduce the susceptibility of the virus to other CpTAs. The virus of the test subjects will need to be sequenced prior to treatment initiation, and monitored during and after treatment in future clinical studies. Taken together, these results support further clinical investigation of Canocapavir as a potent therapeutic agent for treating patients with CHB.