NORCROSS, Ga., April 30, 2020 (GLOBE NEWSWIRE) -- Galectin Therapeutics, Inc. (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins, today announced that it has submitted to the U.S. Food and Drug Administration (FDA) its protocol for a seamless adaptively-designed Phase 2b/3 clinical study, the NASH-RX trial, evaluating the safety and efficacy of its galectin-3 inhibitor, belapectin (GR-MD-02), for the prevention of esophageal varices in patients with non-alcoholic steatohepatitis (NASH) cirrhosis.

The filing anticipates clinical trials will begin in the second quarter of this year. The major features of the innovative, seamless adaptively-designed Phase 2b/3 study design are summarized below and graphically depicted in the figure:

• In patients with NASH cirrhosis and clinical signs of portal hypertension but without esophageal varices at baseline, this trial will assess the effect of belapectin on the incidence of new varices (the primary endpoint) – as well as assessing the effect on the incidence of long-term, clinically significant cirrhosis-related “hard” outcomes (a key secondary efficacy endpoint).
• The design of this trial reflects the unmet medical needs of the target patient population for belapectin treatment: NASH patients with compensated cirrhosis who develop esophageal varices. Bleeding varices are a cause of death in about one-third of cirrhotic patients. There is no approved treatment for preventing varices in these patients. The development of new varices reflects the progression of hepatic cirrhosis and thus portends the development of other cirrhosis complications and outcomes such as significant ascites, hepatic encephalopathy, and ultimately liver failure.
• During the first 18 months of the trial, two belapectin dose levels (2 mg/kg LBM and 4 mg/kg LBM) will be compared to placebo. Then, at the interim analysis (IA), one belapectin dose will be selected based on efficacy and safety, for continued evaluation in Stage 2 (Phase 3). Prior trials have demonstrated the safety of belapectin with doses of up to 8 mg/kg for 52 weeks (Phase 2b Study GT-026).

“The protocol filed today reflects the previous feedback received from the FDA, as well as key contributions from Dr. Naga Chalasani and Dr. Stephen Harrison, NASH opinion leaders who are co-primary investigators for the study, biostatistical experts and numerous other collaborators at Covance, our CRO,” said Harold H. Shlevin, Ph.D., President and Chief Executive Officer of Galectin Therapeutics. “We are very grateful for all of their efforts, and for the previous feedback and suggestions from the FDA. The study design has been modified and further refined such that it provides for a prespecified interim analysis (IA). The IA of efficacy and safety data will be conducted after all planned subjects in Phase 2b component have completed at least 78 weeks (18 months) of treatment and a gastro-esophageal endoscopic assessment. The purpose of the IA is to allow potential seamless adaptive modifications of the study, including: (1) the selection of the optimal dose of belapectin for Phase 3; (2) the re-estimation of the study sample size for Phase 3 portion of the trial; (3) the re-evaluation of the randomization ratio for the Phase 3 portion of the trial; (4) the refinement of the inclusion and exclusion criteria for the Phase 3 portion of the trial, including the CTP status; (5) and/or termination of the study for overwhelming efficacy or futility.

The new trial design also minimizes invasive testing requirements, which we believe will enhance the enrollment and retention of patients. It also provides for a seamless transition of patients from the phase 2b component into the phase 3 stage, as well as provides for the potential addition of new patients. The trial design preserves the surrogate end-point concepts previously discussed with the FDA.

As previously communicated, this is a uniquely challenging time to start a new clinical trial, and we are doing everything in our direct control to prepare for the initiation of the study later this quarter; however, factors beyond our control, specifically related to the COVID-19 pandemic, may delay the trial’s initiation. Notwithstanding that, we remain optimistic in moving forward. The unmet medical need for effective treatment for patients with NASH cirrhosis remains an important motivation.

The trial, entitled “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 now posted on www.clinicaltrials.gov (NCT04365868). Galectin Therapeutics will share more details about the protocol at the time the clinical trial begins. In addition, the FDA has received Galectin’s protocol for the hepatic impairment study which will be conducted in subjects with normal hepatic function and subjects with varying degrees of hepatic impairment (NCT04332432). This filing anticipates that this study will also begin in the second quarter of this year.

About Belapectin (GR-MD-02)

Belapectin is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of fatty liver disease 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. The drug binds to galectin proteins and disrupts their function. Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis.

About Fatty Liver Disease with Advanced Fibrosis and Cirrhosis

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 hepatocytes 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 1-2 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 8,890 liver transplants are performed annually in the U.S. There are no drug therapies approved for the treatment of liver fibrosis or cirrhosis.

About Galectin Therapeutics

Galectin Therapeutics is dedicated to developing novel therapies to improve the lives of patients with chronic liver disease and cancer. Galectin’s lead drug belapectin is a carbohydrate-based drug that inhibits the galectin-3 protein which is directly involved in multiple inflammatory, fibrotic, and malignant diseases, for which it has Fast Track designation by the U.S. Food and Drug Administration. The lead development program is in non-alcoholic steatohepatitis (NASH) with cirrhosis, the most advanced form of NASH-related fibrosis. This is the most common liver disease and one of the largest drug development opportunities available today. Additional development programs are in treatment of combination immunotherapy for advanced melanoma and other malignancies. Advancement of these additional clinical programs is largely dependent on finding a suitable partner. Galectin seeks to leverage extensive scientific and development expertise as well as established relationships with external sources to achieve cost-effective and efficient development. Additional information is available at www.galectintherapeutics.com.