NASH cirrhosis treatment successful in patients without esophageal varices

Galectin Therapeutics announced that its proprietary compound GR-MD-02 significantly reduced hepatic venous pressure gradient in patients with nonalcoholic steatohepatitis-related cirrhosis without esophageal varices in a recent phase 2b trial.

Peter G. Traber, MD
Peter G. Traber

“Patients with cirrhosis without varices is both an easily identifiable population and the population that you want to focus on for treatment because they’re not so far gone that they are going to have complications right away from their cirrhosis,” Peter G. Traber, MD, president and CEO of Galectin, told Healio.com/Hepatology. “But they have cirrhosis, and if you don’t treat them, they will progress.”

The primary endpoint of the NASH-CX phase 2b trial for GR-MD-02 was reduced hepatic venous pressure gradient (HVPG) in patients with well-compensated NASH-related cirrhosis. GR-MD-02 is a galectin-3 inhibitor designed to reverse fibrosis, reduce cell death and inflammation, and decrease portal pressure of cirrhosis.

The trial comprised 161 patients with NASH-related cirrhosis. Fifty-four patients received 2 mg/kg of GR-MD-02 every other week for 1 year, 54 received 8 mg/kg, and another 54 received placebo. Eighty-one of the enrolled patients had esophageal varices at baseline.

Mean patient age was 59 years (range, 52-65 years), 70% were women and 81% were white.

While the difference in HVPG reduction did not reach statistical significance among patients with esophageal varices, there was a positive trend among all patients treated with GR-MD-02 and those without esophageal varices achieved clinically significant outcomes.

“It’s estimated that there at between 3 and 5 million people in the United States with NASH cirrhosis. If 50% of those have no varices, that’s a big number,” Traber said. “If you can prevent people from progressing to varices, that would be a huge drug, both in terms of numbers and in terms of utilization of the drug.”

The researchers defined significant responders as those who received 2 mg/kg of GR-MD-02 every other week for 1 year and achieved an absolute reduction in HVPG of either 2 mmHg or more or 20% or more form baseline.

Compared with the placebo control group, responder patients without esophageal varices had a significant reduction of HVPG (44% vs. 15%; P < .02). Similarly, based on a 20% or more reduction of HVPG from baseline, responder patients without esophageal varices had a greater reduction than the placebo group (40% vs. 15%; P = .03).

GR-MD-02 was well-tolerated and the researchers observed no safety concerns during the trial. Ten patients discontinued the trial prior to end of treatment.

“We’re quite pleased with it,” Traber concluded. “The [key opinion leaders] are excited about it — excited about it to the point that they want to have an extension trial so that the patients that were on placebo can get the drug. This is a large, easily addressable population where if you are able to prevent the development of varices would be a huge clinical benefit.”

Reference: www.galectintherapeutics.com

Disclosure: Traber is an employee of Galectin.

Galectin Therapeutics announced that its proprietary compound GR-MD-02 significantly reduced hepatic venous pressure gradient in patients with nonalcoholic steatohepatitis-related cirrhosis without esophageal varices in a recent phase 2b trial.

Peter G. Traber, MD
Peter G. Traber

“Patients with cirrhosis without varices is both an easily identifiable population and the population that you want to focus on for treatment because they’re not so far gone that they are going to have complications right away from their cirrhosis,” Peter G. Traber, MD, president and CEO of Galectin, told Healio.com/Hepatology. “But they have cirrhosis, and if you don’t treat them, they will progress.”

The primary endpoint of the NASH-CX phase 2b trial for GR-MD-02 was reduced hepatic venous pressure gradient (HVPG) in patients with well-compensated NASH-related cirrhosis. GR-MD-02 is a galectin-3 inhibitor designed to reverse fibrosis, reduce cell death and inflammation, and decrease portal pressure of cirrhosis.

The trial comprised 161 patients with NASH-related cirrhosis. Fifty-four patients received 2 mg/kg of GR-MD-02 every other week for 1 year, 54 received 8 mg/kg, and another 54 received placebo. Eighty-one of the enrolled patients had esophageal varices at baseline.

Mean patient age was 59 years (range, 52-65 years), 70% were women and 81% were white.

While the difference in HVPG reduction did not reach statistical significance among patients with esophageal varices, there was a positive trend among all patients treated with GR-MD-02 and those without esophageal varices achieved clinically significant outcomes.

“It’s estimated that there at between 3 and 5 million people in the United States with NASH cirrhosis. If 50% of those have no varices, that’s a big number,” Traber said. “If you can prevent people from progressing to varices, that would be a huge drug, both in terms of numbers and in terms of utilization of the drug.”

The researchers defined significant responders as those who received 2 mg/kg of GR-MD-02 every other week for 1 year and achieved an absolute reduction in HVPG of either 2 mmHg or more or 20% or more form baseline.

Compared with the placebo control group, responder patients without esophageal varices had a significant reduction of HVPG (44% vs. 15%; P < .02). Similarly, based on a 20% or more reduction of HVPG from baseline, responder patients without esophageal varices had a greater reduction than the placebo group (40% vs. 15%; P = .03).

GR-MD-02 was well-tolerated and the researchers observed no safety concerns during the trial. Ten patients discontinued the trial prior to end of treatment.

“We’re quite pleased with it,” Traber concluded. “The [key opinion leaders] are excited about it — excited about it to the point that they want to have an extension trial so that the patients that were on placebo can get the drug. This is a large, easily addressable population where if you are able to prevent the development of varices would be a huge clinical benefit.”

Reference: www.galectintherapeutics.com

Disclosure: Traber is an employee of Galectin.