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Galectin-3 inhibitor improves hepatic ballooning in NASH

PARIS — GR-MD-02, a novel galectin-3 protein, did not improve hepatic venous pressure gradient in patients with nonalcoholic steatohepatitis and cirrhosis; however, the inhibitor did significantly improve hepatocyte ballooning, according to a presentation at the International Liver Congress 2018.

“Change in [hepatic venous pressure gradient (HVPG)] associated with GR treatment was not significant in total patient population, but statistically significant in the pre-specified group of mild portal hypertension,” Naga Chalasani, MD, from the Indiana University School of Medicine, said in his presentation. “In patients without varices at baseline, there was a statistically significant difference in the [2 mg/kg] group in the change in HVPG, percentage of responders, and development of new varices.”

To test the safety and efficacy of GR-MD-02, Chalasani and colleagues randomly assigned 162 patients with NASH-related cirrhosis and portal hypertension to receive biweekly intravenous infusions of GR-MD-02 at 2 mg/kg (n = 54), 8 mg/kg (n = 54) or placebo (n = 54) for 52 weeks.

Baseline demographic, clinical and laboratory characteristics, and mean HVPG were similar among the three groups.

While the researchers observed no significant effect on fibrosis or nonalcoholic fatty liver disease activity score among the three groups, patients who received 2 mg/kg of GR-MD-02 had a significant improvement in hepatocyte ballooning compared with placebo. Patients who received 8 mg/kg demonstrated a nonsignificant trend toward improved hepatocyte ballooning.

Additionally, significantly fewer patients who received 2 mg/kg (P = .02) developed new varices between baseline and end of treatment compare with placebo.

Both 2 mg/kg and 8 mg/kg doses of GR-MD-02 were well-tolerated and had similar proportions of adverse events and severe adverse events. Three patients from the 8 mg/kg group discontinued treatment due to an adverse event.

“GR treatment improved hepatocyte ballooning in the total, which correlated with an improvement in HVPG. Less pronounced effects of GR [8 mg/kg] may be explained by its variable pharmacokinetics,” Chalasani concluded. “These results warrant further trials with GR-MD-02 in compensated NASH cirrhotic patients without esophageal varices or those with mild portal hypertension.” – by Talitha Bennett

For more information:

Chalasani N, et al. LB-001. Presented at: International Liver Congress; Apr. 11-15, 2018; Paris, France.

Disclosure: Chalasani reports he is a consultant for AbbVie, Afimmune, Allergan/Tobira, Ardelyx, Lilly, Madrigal, NuSirt and Shire; and received grant or research support from Cumberland, Galectin, Gilead, Intercept and Lilly.

Editor’s note: This item has been updated with clarifications from the presenter.