Breakthrough MASH Treatment: ASC41 Shows Promising Results in Reducing Liver Fat

Introduction: Promising Results for ASC41

Gannex Pharma Co., Ltd., a subsidiary of Ascletis Pharma, recently presented interim results from a Phase II clinical trial of ASC41 at the EASL Congress 2024. The study focused on patients with metabolic dysfunction-associated steatohepatitis (MASH), revealing notable reductions in liver fat content after 12 weeks of treatment.

Significant Reduction in Liver Fat

One of the key highlights of the interim results was a 68.2% mean relative reduction in liver fat content from baseline in patients treated with ASC41. This significant reduction is crucial as high liver fat levels are a marker of worsening liver disease.

The reductions were measured using magnetic resonance imaging proton density fat fraction (MRI-PDFF), a reliable method for assessing liver fat. Impressively, 93.3% of patients showed at least a 30% reduction in liver fat content.

Improvement in Liver Enzymes and Lipid Levels

In addition to reducing liver fat, ASC41 treatment led to significant drops in liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These enzymes are markers of liver inflammation and damage, and their reduction indicates an improvement in liver health.

Furthermore, ASC41 demonstrated the ability to lower lipid levels, including LDL-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). These improvements can lower the risk of cardiovascular events, which are common complications in patients with liver diseases.

Excellent Safety and Tolerability Profile

Safety is a critical aspect of any new treatment, and ASC41 performed well in this domain. The Phase II trial revealed that the drug was generally well-tolerated among patients. Adverse events were mainly mild (grade 1) and included those in the placebo group, with no serious treatment-related adverse events reported.

Notably, ASC41 showed excellent gastrointestinal (GI) tolerability, an important consideration for long-term medication use.

About ASC41 and Its Development

ASC41 is a once-daily oral tablet designed as a liver-targeted small molecule. It works by converting into ASC41-A, a potent and selective thyroid hormone receptor β (THRβ) agonist. This specificity is essential for targeted treatment with minimal side effects.

Developed using Ascletis' proprietary technology, ASC41 has already passed three Phase I studies in China and a Phase I study in the U.S., demonstrating no significant drug-drug interactions and consistent drug exposure across different populations.

Details of the Phase II Clinical Trial

The Phase II trial, conducted in China, aims to enroll 180 biopsy-confirmed MASH patients. Participants are randomized into two treatment cohorts receiving either 2 mg or 4 mg of ASC41 daily, alongside a placebo-controlled group, for 52 weeks. The primary goal is to achieve a histological reduction in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) by at least 2 points without worsening fibrosis.

Secondary objectives include MASH resolution and fibrosis improvement. The interim results are based on the first 42 patients who completed 12 weeks of treatment, providing a promising outlook for the overall study.

Conclusion and Future Prospects

Dr. Jinzi J. Wu, CEO of Ascletis, expressed optimism about ASC41's potential to become a best-in-class treatment for MASH. The company looks forward to further data from the ongoing trial to confirm these interim findings.

Overall, ASC41 shows great promise in addressing the unmet medical needs of MASH patients, offering hope for effective management of this challenging liver condition.