Galectin Therapeutics' Belapectin Shows Sustained Antifibrotic Effects in MASH Cirrhosis Through 36 Months

Galectin Therapeutics查看公司主页 presented compelling long-term data from its Phase 2b NAVIGATE trial at the American Association for the Study of Liver Diseases (AASLD) 2025 Annual Meeting, demonstrating sustained antifibrotic effects of belapectin查看药品详情 in patients with compensated MASH cirrhosis (搜索)搜索该疾病 and portal hypertension (搜索)搜索该疾病. The galectin-3 (搜索)搜索该靶点 inhibitor showed consistent disease-modifying potential across multiple biomarkers and clinical endpoints through 36 months of treatment.

Clinical Efficacy Across Risk Categories

The global Phase 2b NAVIGATE trial (NCT04365868查看临床试验) enrolled 355 patients with compensated MASH cirrhosis (搜索)搜索该疾病 and portal hypertension (搜索)搜索该疾病 in a randomized, double-blind, placebo-controlled study. Patients received intravenous belapectin查看药品详情 at 2 mg/kg or 4 mg/kg of lean body mass or placebo every other week for 18 months.

When stratified using FDA-approved Enhanced Liver Fibrosis (搜索)搜索该疾病 (ELF) score cutoffs, belapectin查看药品详情 2 mg/kg demonstrated consistently lower incidence of new varices across all fibrosis categories. The most pronounced benefit occurred in patients with ELF scores >11.3, representing those at highest risk for liver complications, where new variceal development was reduced from 42.9% with placebo to 22.7% with belapectin 2 mg/kg.

The complete ELF stratification results showed:

• ELF score <9.8 (low risk): 17.6% placebo vs 4.8% belapectin 2 mg/kg
• ELF score 9.8-11.3 (mid risk): 18% placebo vs 9.4% belapectin 2 mg/kg
• ELF score >11.3 (highest risk): 42.9% placebo vs 22.7% belapectin 2 mg/kg

Biomarker Evidence Supports Antifibrotic Activity

Multiple biomarker analyses provided mechanistic evidence of belapectin查看药品详情's antifibrotic effects. Pro-C3 (搜索)搜索该靶点 fibrosis biomarker analysis showed comparable baseline levels across treatment groups (placebo: 50.2 ng/mL; 2 mg/kg: 45.9 ng/mL; 4 mg/kg: 43.4 ng/mL). At 78 weeks, patients receiving belapectin 2 mg/kg achieved a mean −6.4 ng/mL reduction in Pro-C3, representing more than 50% improvement from baseline compared with placebo (−4.5 ng/mL).

YKL-40查看药品详情 analysis, a biomarker associated with galectin-3 (搜索)搜索该靶点 upregulation in fibrotic liver disease, demonstrated that 33.8% of patients receiving belapectin查看药品详情 2 mg/kg achieved a ≥20% reduction compared with 23.1% receiving placebo. These findings provide additional mechanistic evidence of galectin-3 pathway modulation.

PRO-C4 (搜索)搜索该靶点 biomarker analysis, associated with liver injury and fibrogenesis, showed that ≥20% increases from baseline occurred at higher rates in placebo-treated subjects compared with those receiving belapectin查看药品详情 2 mg/kg (13% vs 3%), indicating ongoing fibrotic progression in the placebo arm.

Sustained Long-Term Benefits

Extended follow-up data presented in a separate poster showed that the reduction in esophageal variceal development observed at 18 months was sustained through 36 months. Among 57 subjects who completed 36 months of therapy, the cumulative incidence of new varices was 23.4% for placebo, 12.4% for belapectin查看药品详情 2 mg/kg, and 16.7% for belapectin 4 mg/kg.

Using established criteria for clinically meaningful worsening, a lower proportion of patients treated with belapectin查看药品详情 2 mg/kg experienced ≥30% or ≥5 kPa increases in liver stiffness by FibroScan compared with placebo, indicating slowing of fibrosis progression and stabilization of liver function.

Safety Profile and Expert Commentary

The safety profile of belapectin查看药品详情 remained favorable throughout the study period, with incidence of adverse events and serious adverse events comparable across all three cohorts. Rates of discontinuation, adverse events, and serious adverse events were comparable to placebo, with no drug-related serious adverse events reported.

"The long-term NAVIGATE data presented at AASLD provide important insights into the potential of galectin-3 (搜索)搜索该靶点 inhibition in advanced fibrosis," stated Dr. Raj Vuppalanchi, Professor of Medicine and Director of Hepatology at Indiana University School of Medicine. "The sustained improvements in liver stiffness and multiple serum biomarkers, including ELF, PRO-C3 (搜索)搜索该靶点, and YKL-40查看药品详情, are particularly noteworthy, as they collectively suggest a consistent antifibrotic effect and stabilization of disease."

Dr. Khurram Jamil, Chief Medical Officer at Galectin Therapeutics查看公司主页, emphasized the consistency observed across endpoints: "The 2 mg/kg dose demonstrated a clear and clinically meaningful reduction in the incidence of new varices across all ELF risk categories, with the strongest effect seen in patients at highest risk for liver complications."

Addressing Unmet Medical Need

MASH cirrhosis (搜索)搜索该疾病 represents a significant unmet medical need, with no approved therapeutic options currently available for patients. Joel Lewis, Chief Executive Officer at Galectin Therapeutics查看公司主页, noted that these results "represent an important milestone for the belapectin查看药品详情 program and for patients living with MASH cirrhosis, a population with no approved therapeutic options today."

Belapectin查看药品详情 is a carbohydrate-based drug that inhibits the galectin-3 (搜索)搜索该靶点 protein, which is directly involved in multiple inflammatory, fibrotic, and malignant diseases. The therapy has received Fast Track designation from the U.S. Food and Drug Administration for its development program in MASH with cirrhosis.