Galectin Therapeutics Submits Seamless Adaptively-Designed Phase 2b/3 NASH-RX Protocol in NASH Cirrhosis

The first patient currently expected to be enrolled in the second quarter of 2020

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.