Chiglitazar MASH Phase II Study to be Presented at 2024 Liver Disease Meeting

On October 15, 2024, the American Association for the Study of the Liver (AASLD) unveiled the names of the individuals selected to present oral reports at its annual meeting. This year's event, set to take place in San Diego, USA from November 15th to 19th, will feature an abstract from a Phase II clinical trial (CGZ203) concerning the treatment of non-alcoholic steatohepatitis (NASH), also known as metabolic associated steatohepatitis (MASH). The study focuses on Chiglitazar (Carfloglitazar), a drug developed independently by Shenzhen Chipscreen Biosciences.

Metabolic associated fatty liver disease (MAFLD) affects over 25% of the population in China, with about a quarter of these patients developing MASH. The incidence is even higher among those with metabolic syndrome. Currently, there is only one approved drug globally, a thyroid hormone receptor beta agonist, for the treatment of MASH, and China has not approved any medications for this condition.

The CGZ203 trial is a randomized, double-blind, placebo-controlled Phase II study designed to assess the safety and preliminary efficacy of Chiglitazar in treating MASH. Participants diagnosed with MASH were randomly divided into three groups to receive either 48mg (n=42), 64mg (n=41) of Chiglitazar, or a placebo (n=21). The treatment was administered orally once daily over 18 weeks.

The trial results indicated a significant reduction in liver fat content (LFC), measured by MRI-PDFF, among those treated with Chiglitazar. Specifically, there was a 28.1% reduction with the 48mg dose and a 39.5% reduction with the 64mg dose, compared to a 3.2% reduction in the placebo group. Furthermore, 40.5% of patients in the 48mg group and 65.9% in the 64mg group achieved over a 30% decrease in LFC, compared to just 14.3% in the placebo group. Additionally, plasma biochemical markers related to chronic inflammation and liver injury, such as CK-18, liver transaminase, and bilirubin, showed substantial decreases after Chiglitazar treatment. Notably, the alanine aminotransferase (ALT) levels in the high-dose group dropped by more than 50% from baseline, with over 70% of these patients' ALT levels returning to the normal range.

Liver fibrosis, assessed using Fibroscan LSM, showed a dose- and time-dependent reduction in liver stiffness values, with the high-dose group experiencing a 2 Kpa decrease after 18 weeks. Compared to the placebo, the Chiglitazar groups exhibited similar safety profiles. Concerning potential side effects related to PPAR agonists, there was no significant weight gain in the Chiglitazar groups, with a slight weight decrease in the high-dose group, and only one mild case of edema in the low-dose group.

This study highlights Chiglitazar's favorable safety and initial efficacy in addressing multiple pathological aspects such as liver fat accumulation, chronic inflammation, and liver fibrosis in MASH patients. Further clinical trials are needed to confirm these findings.

Chiglitazar is a novel hypoglycemic drug developed by Chipscreen Biosciences, the first fully PPAR agonist approved for type 2 diabetes management globally. Chiglitazar targets insulin resistance, a key factor in type 2 diabetes, and activates all three PPAR subtypes to balance glucose, lipid, energy, and protein metabolism. Initial clinical studies have shown that Chiglitazar is effective in regulating blood glucose, lipids, and energy in type 2 diabetes patients, with a good safety profile.

Chipscreen Biosciences is a pioneering drug development company in China that leverages advanced technology platforms to create innovative drugs for a range of conditions, including cancer, metabolic diseases, autoimmune diseases, central nervous system disorders, and antiviral treatments. With a robust global presence and numerous patents, the company continues to lead the field in drug innovation and development.