Belapectin may help reduce liver scarring in those with severe MASH
New trial data also show lower risk of complications with infusion therapy
Galectin Therapeutics‘ experimental medication belapectin may help reduce liver scarring, or fibrosis, and lower the risk of blood vessel complications in people with metabolic-associated steatohepatitis (MASH) and compensated cirrhosis, or irreversible liver fibrosis.
That’s according to new data from the Phase 2 NAVIGATE clinical trial, which show that “belapectin demonstrated consistent, meaningful effects across multiple key biomarkers in MASH cirrhosis,” per the developer.
MASH is a severe form of fatty liver disease, a condition marked by the buildup of fat in the liver. Compensated cirrhosis refers to irreversible liver scarring that still allows the liver to function properly.
“The new NAVIGATE data … further strengthen the clinical and mechanistic profile of belapectin. We continue to see encouraging consistency across key biomarkers … supporting belapectin’s durable antifibrotic activity and potential to slow disease progression in patients with compensated MASH cirrhosis,” Joel Lewis, CEO and president of Galectin, said in a company press release announcing business updates and its latest financial results.
Galectin has submitted NAVIGATE results to the U.S. Food and Drug Administration (FDA), seeking feedback on plans for next steps in belapectin’s development. The company said it expects to hear from the FDA by year’s end.
“As we move forward, our focus remains on advancing dialogue with FDA and exploring strategic opportunities to maximize the value of this promising program,” Lewis said.
In MASH, the accumulation of fat in the liver triggers inflammation and fibrosis. Liver fibrosis can progress to cirrhosis and interfere with the normal blood flow through the organ, leading to increased blood pressure in the liver’s main vein — a condition called portal hypertension.
This can cause blood to be redirected to smaller veins elsewhere in the body, particularly in the esophagus (food pipe), resulting in esophageal varices. These are are enlarged esophageal veins that are at risk of rupturing and causing life-threatening bleeding.
Bleeding from esophageal varices is reported to be the cause of death in about one-third of all people with cirrhosis.
Belapection failed to meet main goal in NAVIGATE clinical trial
Belapectin, an infusion therapy, is designed to reduce liver fibrosis and decrease the risk of esophageal varices by blocking the activity of a fibrosis-driving protein called galectin-3.
NAVIGATE (NCT04365868) enrolled more than 350 adults with MASH and compensated cirrhosis. All participants also had clinical signs of portal hypertension, but did not have varices when they enrolled.
The participants were randomly assigned to receive either one of two doses of belapectin (2 or 4 mg/kg) or a placebo, administered into the bloodstream every other week for about 1.5 years.
The study’s main goal was to see if the treatment was superior to the placebo in reducing rates of esophageal varices. Secondary goals included lower rates of variceal bleed requiring treatment or hospitalization and other complications of cirrhosis, as well as liver transplant and death. The researchers also assessed changes in liver stiffness, which is a marker of liver fibrosis, and also of the therapy’s safety.
Galectin announced last year that the trial had missed its main goal. While the rate of esophageal varices was 43.2% lower among people treated with the 2 mg/kg belapectin dose, compared with those given the placebo, the difference wasn’t statistically significant, meaning it’s mathematically plausible that the benefits seen may be due to random chance.
Nonetheless, some promising trends were seen with the medication’s use. The company further examined these results.
But new analyses show reductions over 50% in marker of liver scarring
In the new analyses, the rates of esophageal varices were compared across different Enhanced Liver Fibrosis (ELF) scores; ELF is a noninvasive blood test used to assess liver fibrosis.
The results showed lower rates of varices with 2 mg/kg belapectin compared with placebo across all ELF score categories. The largest difference was observed among patients with more severe fibrosis (22.7% vs. 42.9%).
The new results also showed that participants given 2 mg/kg belapectin had more than 50% greater reductions in Pro-C3, a marker of fibrosis. Those on the therapy were also less likely to experience a substantial increase in levels of PRO-C4, a marker of liver injury. Meanwhile, treated patients were more likely to experience reductions in YKL-40, a marker of inflammation.
“The 2 mg/kg dose demonstrated a clear and clinically meaningful reduction in the incidence of new varices across all ELF risk categories, with the strongest effect seen in patients at highest risk for liver complications,” Khurram Jamil, MD, Galectin’s chief medical officer, said in a separate press release that detailed the new results.
“In addition, the more than 50% greater reduction in Pro-C3 levels versus [the] placebo further supports belapectin’s antifibrotic activity and alignment between biomarker and clinical outcomes,” Jamil said.
Other analyses indicated that participants given 2 mg/kg belapectin were less likely than those given the placebo to have clinically significant portal hypertension (CSPH) and to experience liver decompensation, when the liver can no longer work as it should.
Taken together, these findings strengthen our confidence in belapectin’s mechanism of action and its potential to positively impact disease progression in this high-risk population.
Over 1.5 years, a higher proportion of belapectin-treated participants transitioned from the CSPH or probable CSPH categories to the no/low-risk category, relative to those on the placebo, the data showed.
In addition, approximately 32% fewer patients treated with belapectin’s 2 mg/kg dose experienced at least a 20% worsening in the AGILE-4 assessment, a threshold indicative of an increased risk of liver complications.
“This improvement reflects a meaningful reduction in disease progression and is consistent with the clinical … findings of a lower incidence of new varices in the NAVIGATE trial,” the release stated.
According to Jamil, these results are “particularly encouraging” as the study population have severe MASH cirrhosis.
“Taken together, these findings strengthen our confidence in belapectin’s mechanism of action and its potential to positively impact disease progression in this high-risk population,” Jamil said.
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