Ascletis announced the dosing of the first cohort of healthy subjects in the ASC42 bridging study in China for chronic hepatitis B (CHB) indication. ASC42 is an in-house developed, novel non-steroidal, selective, potent FXR agonist with best-in-class potential.
On June 7, 2021, Ascletis announced that China National Medical Products Administration (NMPA) had approved the Investigational New Drug (IND) application for ASC42 to conduct clinical trials in China for CHB indication.
On June 16, 2021, Gannex, a wholly owned company of Ascletis announced ASC42 positive topline results of safety and pharmacodynamic biomarkers from the US phase I trial of NASH indication. The data indicated that there were no pruritus observed during 14-day treatment of the once-daily human therapeutic dose of 15 mg and no treatment-emergent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations during 14-day, once daily treatment with 15 mg.
Based on the pharmacokinetic data from the ASC42 phase I trial in 64 healthy subjects in the US, the bridging study in China is a randomized, placebo-controlled, double-blind single-ascending dose (5 mg and 15 mg) study in 30 healthy subjects receiving ASC42 or matching placebo. The objective of the bridging study is to select doses for the upcoming phase II trial in China in patients with CHB.
As an FXR agonist, ASC42 has unique mechanism of action against hepatitis B virus (HBV): ASC42 inhibits the transcription of HBV cccDNA into HBV RNA, which in turn inhibits the translation of HBV RNA into HBsAg. ASC42 may also reduce HBV cccDNA stability. Both in vitro primary human hepatocyte (PHH) cells and in vivo AAV/HBV mouse studies demonstrated that ASC42 significantly inhibited serum hepatitis B surface antigen (HBsAg) and HBV pregenomic RNA (pgRNA), indicating that ASC42 has therapeutic potential to functionally cure CHB.
“We are excited about moving FXR agonist ASC42 into CHB indication,” said Dr. Jinzi J. Wu, founder, chairman and CEO of Ascletis, “Dosing the first cohort subjects in China for CHB indication is achieved merely one month after receiving China NMPA's IND approval. This demonstrates again the execution excellence of our clinical development team.”