Galectin Therapeutics' stock plummeted after its Phase IIb/III NAVIGATE trial failed to achieve its primary endpoint. The trial assessed belapectin in patients with metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis and portal hypertension, aiming to prevent the development of esophageal varices. Although belapectin demonstrated a reduction in varices incidence, the results did not reach statistical significance compared to the placebo group.
The NAVIGATE trial enrolled patients with MASH cirrhosis and high blood pressure in the portal vein. Patients were administered either 2 mg/kg or 4 mg/kg doses of Belapectin. The primary endpoint was the prevention of varices, enlarged veins in the esophagus that may occur in people with cirrhosis of the liver. While both doses of belapectin reduced the incidence of varices in the intent-to-treat population, the difference over placebo was not statistically significant.
Galectin Therapeutics highlighted the per-protocol population, consisting of patients who completed 18 months of therapy with upper endoscopy at the beginning and end of the study. In this group, the incidence of varices was reduced by 48.9%, still short of the targeted 52.5% reduction.
According to the company, the safety profile of belapectin remains "highly encouraging," with adverse events and discontinuation rates across both dosage groups comparable to placebo. The company notes that as a sugar-like structure, the drug has low toxicity potential because it is metabolized to relatively harmless compounds.
Belapectin functions by blocking galectin-3, a protein involved in inflammation, cell growth, and fibrosis. Earlier studies have shown promise, with a Phase I study combining belapectin with Keytruda demonstrating a 50% response rate in advanced melanoma.
Naga Chalasani, a professor at Indiana University School of Medicine involved in belapectin's development, stated that the drug "clearly is offering a reproducible benefit and should be continued in clinical development."
Galectin Therapeutics is continuing to analyze the trial data and awaiting 36-month outcomes, expected in early 2025. The company will then determine the next steps for belapectin's development.
