Galectin Therapeutics Inc. announced that in late December 2022, it ended the enrollment of new patients into NAVIGATE, its seamless, adaptive, phase 2b/3 study of belapectin in patients with liver cirrhosis caused by non-alcoholic steatohepatitis (NASH). The last patient was randomized into NAVIGATE at the end of February 2023. In order to be randomized, the screening process documented the presence of clinical signs of portal hypertension and validated the absence of esophageal and/or gastric varices by a central adjudication of video recording of upper esophago-gastric endoscopies.

NAVIGATE has randomized 357 patients, above its initial objective of approximately 315 patients. NAVIGATE is the first study of its kind and is a global effort that recruited patients in 14 countries and on five continents. The main efficacy objective is the primary prevention of esophageal varices.

Patients enrolled in the study have cirrhosis caused by NASH and, because of the advancing cirrhotic process, have already developed portal hypertension but have not yet developed dilated veins in the esophagus known as esophageal varices, a clinically concerning complication of portal hypertension. Portal hypertension is the consequence of the unrelented inflammatory and fibrotic process occurring in the liver and dramatically increases the risk of developing esophageal varices, a potentially life-threatening complication of liver cirrhosis. Belapectin is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of NASH and fibrosis.

Galectin-3 plays a major role in diseases that involve scarring of organs, including fibrotic disorders of the liver, lung, kidney, heart and vascular system. Belapectin binds to galectin-3 and disrupts its function. Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis.

A Phase 2 study showed belapectin may prevent the development of esophageal varices in NASH cirrhosis, and these results provide the basis for the conduct of the NAVIGATE trial. The NAVIGATE trial, titled “A Seamless Adaptive Phase 2b/3, Double-Blind, Randomized, Placebo-controlled Multicenter, International Study Evaluating the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis,” is posted on  (NCT04365868). Galectin-3 has a significant role in cancer, and the Company has supported a Phase 1b study in combined immunotherapy of belapectin and KEYTRUDA in advanced melanoma and in head and neck cancer.

This trial provided a strong rationale for moving forward into a Company-sponsored Phase 2 development program, which the company is exploring. Non-alcoholic steatohepatitis (NASH) has become a common disease of the liver with the rise in obesity and other metabolic diseases. NASH is estimated to affect up to 28 million people in the U.S. It is characterized by the presence of excess fat in the liver along with inflammation and hepatocyte damage (ballooning) in people who consume little or no alcohol.

Over time, patients with NASH can develop excessive fibrosis, or scarring of the liver, and ultimately liver cirrhosis. It is estimated that as many as 1 to 2 million individuals in the U.S. will develop cirrhosis as a result of NASH, for which liver transplantation is the only curative treatment available. Approximately 9,000 liver transplants are performed annually in the U.S. There are no drug therapies approved for the treatment of liver fibrosis or cirrhosis.