Fifth Positive DSMB Review for Galectin's NAVIGATE Belapectin Study in MASH-Related Cirrhosis

Galectin Therapeutics, a pioneering company in the development of galectin-3 targeting therapies, has announced a favorable update from its fifth independent data and safety monitoring board (DSMB) meeting. The DSMB has given a green light to the ongoing NAVIGATE study, which is evaluating the drug belapectin for the treatment of cirrhotic portal hypertension due to Metabolic Dysfunction-Associated Steatohepatitis (MASH). The study is designed to be seamless, adaptive, and incorporates a randomized, placebo-controlled, double-blind approach.

The NAVIGATE trial is groundbreaking for its innovative adaptive design and its focus on the prevention of esophageal varices, a clinical sign of portal hypertension and a critical factor in the progression of liver disease. The trial is divided into two stages. The first stage has already enrolled 357 patients exhibiting signs of portal hypertension but without cirrhosis decompensations or esophageal varices. Portal hypertension is a consequence of ongoing inflammation and fibrosis in the liver, significantly increasing the risk of developing esophageal varices, a potentially fatal complication of liver cirrhosis.

Participants in the trial are randomly assigned to receive belapectin at varying dosages or a placebo every two weeks. An interim analysis of the trial's safety and efficacy will be performed after the last patient in the first stage has been monitored for 18 months and undergone a second esophago-gastric endoscopy. The outcome of this analysis will decide whether the study advances to the second stage and which protocol adaptations are implemented.

There are three possible results from the interim analysis: halting the NAVIGATE study due to significant efficacy or lack of it, or moving forward to the second stage with adaptations such as selecting the optimal dose of belapectin and determining the number of new patients needed for the final analysis.

Dr. Pol Boudes, Chief Medical Officer of Galectin Therapeutics, has expressed confidence in the NAVIGATE study's progress and the safety profile of belapectin, which is crucial given the comorbidities and polypharmacy of the trial's patient population. The innovative trial design is seen as a potential catalyst for clinical development in cirrhosis, an area that has seen limited medical advancements in the past half-century. The next DSMB meeting will assess the interim analysis results and provide further recommendations.

Belapectin is a complex carbohydrate that targets galectin-3, a protein implicated in the development of NASH/MASH and fibrosis. It has shown promise in reversing liver fibrosis and cirrhosis in preclinical studies. The drug is also being studied in combination with immunotherapy for advanced melanoma and head and neck cancer.

MASH, previously known as nonalcoholic steatohepatitis (NASH), is a prevalent liver condition linked to obesity and metabolic disorders. It affects an estimated 28 million people in the U.S. and can lead to liver cirrhosis and portal hypertension. Currently, liver transplantation is the only cure for MASH-induced cirrhosis, with approximately 9,000 liver transplants performed annually in the country. There are no approved drug therapies for liver cirrhosis treatment.

Galectin Therapeutics is committed to developing new treatments for chronic liver disease and cancer. The company's lead drug, belapectin, has received Fast Track designation from the U.S. Food and Drug Administration for its potential role in treating MASH with cirrhosis. Additional development programs are focused on combination immunotherapy for head and neck cancers and other malignancies, contingent upon finding suitable partners and securing further clinical development funding.

The company's press release highlights the importance of managing expectations regarding the development and approval of belapectin and other drugs in the pipeline. It acknowledges the inherent uncertainties in clinical trials and the challenges of drug development, including achieving trial endpoints, scaling up manufacturing, and securing additional capital for research and development.