Chipscreen Biosciences' Chiglitazar (Carfloglitazar) has shown promising results in a Phase II clinical trial (CGZ203) for the treatment of metabolic associated steatohepatitis (MASH). The study, a randomized, double-blind, placebo-controlled trial, evaluated the safety and efficacy of Chiglitazar monotherapy in MASH patients.
The trial, which involved patients clinically diagnosed with MASH, randomly assigned participants to receive either Chiglitazar 48mg (n=42), 64mg (n=41), or a placebo (n=21) orally once daily for 18 weeks. The primary endpoint was the change in liver fat content (LFC) as evaluated by MRI-PDFF.
Key Findings on Liver Fat and Inflammation
After 18 weeks of treatment, the Chiglitazar groups demonstrated significant reductions in LFC compared to placebo. Specifically, the 48mg and 64mg Chiglitazar groups experienced LFC decreases from baseline of 28.1% and 39.5%, respectively, while the placebo group showed a decrease of only 3.2%. Furthermore, a notable proportion of patients in the Chiglitazar groups achieved a greater than 30% reduction in LFC: 40.5% in the 48mg group and 65.9% in the 64mg group, compared to 14.3% in the placebo group.
Plasma biochemical indicators related to chronic inflammation and liver injury, including CK-18, liver transaminases, and bilirubin, also significantly decreased following Chiglitazar treatment. In the high-dose group, alanine aminotransferase (ALT) levels decreased by more than 50% from baseline, with ALT levels returning to the normal range in over 70% of patients.
Impact on Liver Fibrosis
Liver fibrosis, assessed by Fibroscan LSM, showed a dose- and time-dependent decrease in liver stiffness values in the Chiglitazar groups. The high-dose group exhibited a decrease of 2 KPa in LSM values after 18 weeks of treatment, suggesting a reduction in liver fibrosis.
Safety and Tolerability
Chiglitazar demonstrated a good safety profile, comparable to placebo. Notably, there was no significant body weight gain in the Chiglitazar treatment groups; in fact, a slight decrease in weight was observed in the high-dose group. Only one mild edema event occurred in the low-dose group.
Clinical Implications
The results suggest that Chiglitazar has the potential to address multiple pathological aspects of MASH, including liver fat accumulation, chronic inflammation, and liver fibrosis. These findings are particularly relevant given the high prevalence of metabolic associated fatty liver disease (MAFLD) in China, where over 25% of the population is affected, with approximately 25% of these individuals progressing to MASH. Currently, only one thyroid hormone receptor beta (THR - β) agonist is approved globally for MASH treatment, and no drugs are yet approved in China for this condition.
Professor You Hong from Beijing Friendship Hospital Affiliated to Capital Medical University presented these findings at the American Association for the Study of the Liver (AASLD) annual meeting on November 17, 2024. The presentation, titled "A randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of Chiglitazar in NASH patients," highlighted the potential of Chiglitazar as a novel treatment for MASH. Further clinical trials are needed to confirm these promising results.
