A study looking at a treatment for primary biliary cholangitis (PBC) has this month (August) enrolled 12 patients and is expected to be completed by the start of this year’s fourth quarter.
Gannex Pharma Co., Ltd., owned by Ascletis Pharma Inc., announced yesterday (August 15) that it had finished its first dosing in the U.S. drug-drug interaction (DDI) study of Farnesoid X Receptor agonist ASC42 for treatment of PBC.
The DDI study and ongoing phase 2 clinical trial in PBC patients in China will provide more evidence to support upcoming phase 3 trials in the U.S., China and the European Union.
Liver transplant
PBC is a chronic autoimmune cholestatic disease and frequently progresses to liver fibrosis and cirrhosis requiring liver transplantation or resulting in death. In response to the increasing incidence, Asian Pacific Association for the Study of the Liver (APASL) developed the clinical practice guidance on the diagnosis and management of patients with PBC in 2022.
PBC is gaining extensive attention as both the incidence and prevalence has showed an increasing tendency globally.
An epidemiology study indicates that there were approximately 120,000 PBC patients in the U.S. in 2014. Ursodeoxycholic acid (UDCA) is the standard treatment for PBC. However, approximately 40% of PBC patients have an inadequate response to, or are unable to tolerate, UDCA.
Pruritus
For those patients with insufficient UDCA response or intolerance, obeticholic acid (OCA) is the only approved medicine in the U.S., but it has not been approved in China yet. Additionally, OCA may significantly cause pruritus and low density lipoprotein cholesterol (LDL-C) levels to rise.
ASC42 is an in-house developed, novel non-steroidal, selective, potent Farnesoid X Receptor (FXR) agonist with potential and global intellectual property.
Previous phase 1 clinical trial in the U.S. demonstrated that ASC42 might be a potentially best-in-class PBC drug candidate as LDL-C levels were in normal range with no pruritus occurrence, and FXR target engagement biomarker FGF19 increased 1,780% when ASC42 was dosed at 15 mg, once daily (QD) during the 14-day treatment.
Currently, FXR agonist ASC42 is in phase 2 clinical trial in China. The study consists of three ASC42 active treatment arms (5 mg, 10 mg and 15 mg) and one placebo control arm at the ratio of 1:1:1:1 and is expected to enroll a total of 100 patients who have an inadequate response to or are unable to tolerate UDCA. The treatment duration is 12 weeks.
Gannex intends to initiate phase 3 clinical trials in China, the U.S. and the EU after the completion of the ongoing phase 2 clinical trial in China.
Fast progress
Jinzi J. Wu, founder, chairman and CEO of Ascletis, said: “It only took us two months to complete the first subject dosing after the application of DDI study was approved by the U.S. FDA. This fast progress, once again, demonstrated the execution excellence of our team.
“Gannex is advancing clinical trials of FXR agonist ASC42 in both China and the U.S. to meet the unmet medical needs for patients with PBC. We are dedicated to improving the current treatments of PBC and providing more options for patients.”
Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Ascletis rapidly advances its drug pipeline with an aim of leading in global competition.