With FDA support, developer planning late-stage trial of belapectin for MASH
Positive results could support approval of Galectin infusion therapy
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With new support from the U.S. Food and Drug Administration (FDA), Galectin Therapeutics is preparing for a late-stage clinical trial to test its therapy candidate belapectin in people with advanced metabolic dysfunction-associated steatohepatitis (MASH), a severe form of steatotic liver disease (SLD).
These initial preparations follow a recent meeting with the regulatory agency regarding the trial’s design, which resulted in an agreed primary goal and a coming together on certain methods to be used, according to the developer.
Galectin said in a company press release that it expects, if the Phase 3 trial meets that main goal, that the results will be sufficient to support FDA approval of belapectin for certain people with MASH. The therapy is being developed for patients with cirrhosis, or irreversible liver scarring, and portal hypertension, meaning high blood pressure in the liver’s main large vein.
“We are pleased to have reached agreement with [the] FDA on the key elements of our planned Phase 3 program for belapectin,” said Joel Lewis, Galectin’s CEO. “Alignment on the study design, primary endpoint, and regulatory framework provides important clarity, as we advance the program with renewed confidence.”
In the meantime, the company is also evaluating potential strategic partnership opportunities regarding belapectin’s development.
“We remain committed to patients with MASH cirrhosis and portal hypertension facing the highest risk of life-threatening [events where liver function worsens], who currently are excluded from enrolling in other ongoing drug development efforts,” Lewis said. “Additionally, [the] FDA acknowledged the substantial unmet medical need in this patient population during our meeting, which strengthened our dedication to continuing the development of belapectin and our Phase 3 trial.”
In MASH, the buildup of liver fat that marks all forms of SLD triggers inflammation and scarring, or fibrosis, in the organ. That can lead to cirrhosis and portal hypertension, with such high blood pressure in turn leading to esophageal varices, or enlarged blood vessels in the esophagus, which is the tube that carries food from the mouth to the stomach. Esophageal varices are prone to tearing, which can lead to life-threatening bleeding.
Infusion therapy showed benefits, but missed main goal in earlier trial
Belapectin is an infusion therapy designed to reduce liver scarring by blocking the activity of a fibrosis-related protein called galectin-3.
An earlier Phase 2b study called NAVIGATE (NCT04365868) tested two doses of the therapy — 2 or 4 mg/kg — against a placebo in more than 350 adults with MASH. All of the participants had compensated cirrhosis, meaning their livers were functioning despite extensive scarring. Each of them also had clinical signs of portal hypertension, but no esophageal varices at the study’s start.
The trial’s main goal was to show that belapectin was better than the placebo at preventing the development of new esophageal varices, but it missed that goal. Rates of varices were generally lower in participants given the 2 mg/kg dose of belapectin compared with those given the placebo, but the difference was not statistically significant. That means it’s mathematically plausible that the difference is due to just random chance.
Nonetheless, in a subset of trial participants who completed 1.5 years in the study and had endoscopy data at its start and end, rates of new varices were significantly lower with the 2 mg/kg belapectin dose than with the placebo. An endoscopy is a minimally invasive procedure in which a long, flexible tube with a tiny light and camera is introduced through the mouth and used to directly view the inside of a body cavity or an organ.
Trial data also indicated that the 2 mg/kg belapectin dose tended to reduce liver stiffness, which is used as a proxy for liver fibrosis.
Trial to test belapectin in patients with cirrhosis, portal hypertension
The upcoming Phase 3 trial is being planned to test a single 2 mg dose of belapectin against a placebo in adults with MASH who have cirrhosis and portal hypertension. Galectin said the study is expected to involve a similar number of participants to the NAVIGATE trial, meaning approximately 350 patients would likely be enrolled.
This trial’s main goal — which the FDA has now backed — will be a composite measure that includes the development of esophageal varices larger than 5 mm (about 0.2 inches). Galectin said other measures will also be included in the composite measure, but the company did not provide specifics.
The FDA has also signaled agreement with Galectin’s plans for a centralized review process to analyze endoscopic readings, which will be used to assess for varices. The company said this protocol will ensure that these assessments are performed consistently for participants across all study sites.
“[The] FDA’s acceptance of our centralized endoscopy review process underscores the scientific rigor and operational robustness of the methodology that Galectin pioneered, and successfully implemented in the NAVIGATE trial,” said Khurram Jamil, MD, Galectin’s chief medical officer. “Standardized, blinded assessment of esophageal varices is critical to ensuring reliable and reproducible outcome evaluation in global studies.”
Galectin plans to submit a final protocol for the upcoming Phase 3 study to the FDA in the coming months.
“Importantly,” according to Jamil, the FDA’s recent feedback “supports the advancement of belapectin [toward] full approval, which we believe offers the opportunity to pursue a broad indication focused on preventing disease progression in patients with MASH cirrhosis.”
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