8-K: Galectin Therapeutics Announces Mixed Results for Belapectin in Cirrhotic Portal Hypertension Trial

Galectin Therapeutics' NAVIGATE trial showed a statistically significant reduction in esophageal varices in a pre-specified patient group treated with belapectin, but failed to reach statistical significance in the overall study population.

Summary

• Galectin Therapeutics announced top-line results from the NAVIGATE clinical trial evaluating belapectin for cirrhotic portal hypertension caused by MASH.
• The trial was a global, multicenter, randomized, double-blind, placebo-controlled study with 355 patients across 15 countries.
• Patients were randomized to receive either 2mg/kg or 4mg/kg of belapectin or a placebo every other week for 18 months.
• The primary endpoint was the prevention of varices, assessed as a composite clinical outcome.
• In the intent-to-treat (ITT) population, there was a 43.2% reduction in varices in the 2mg/kg belapectin group compared to placebo, but this did not reach statistical significance.
• However, in the pre-protocol population (PPP), there was a statistically significant 48.9% reduction in varices in the 2mg/kg belapectin group (p-value < 0.05).
• Liver stiffness, measured by Fibroscan, showed a 50% lower number of subjects with worsening stiffness in the belapectin groups.
• Belapectin was well tolerated with no safety signals, and adverse events were comparable across all groups.
• All enrolled subjects transitioned into a 36-month treatment period, with approximately 50 subjects completing the full 36 months to date.
• Additional data, including biomarker data, is expected in early 2025.

Sentiment

Score: 5

Explanation: The sentiment is mixed due to the statistically significant result in the per-protocol population being offset by the lack of significance in the intent-to-treat population. The positive safety profile and potential for future development are encouraging, but the need for further trials and potential capital raises temper the overall outlook.

Positives

• Belapectin demonstrated a statistically significant reduction in the development of esophageal varices in the pre-protocol population.
• The 2 mg/kg dose of belapectin showed a clear benefit in reducing varices.
• Belapectin was well tolerated with a good safety profile.
• Liver stiffness improved in patients treated with belapectin.
• The trial was conducted across 130 sites in 5 continents, demonstrating a broad reach.

Negatives

• The primary endpoint in the intent-to-treat population did not reach statistical significance.
• The 4 mg/kg dose of belapectin did not show increased efficacy compared to the 2 mg/kg dose.
• The composite endpoint included intercurrent events, which may have impacted the results.

Risks

• The failure to achieve statistical significance in the intent-to-treat population may impact regulatory approval.
• The company may need to conduct further trials to demonstrate efficacy.
• The company may face challenges in securing partnerships for further development.
• The company's ability to continue operations is dependent on managing costs and raising additional capital.
• The company may not be successful in scaling up manufacturing and meeting requirements related to chemistry, manufacturing and control matters.

Future Outlook

Galectin Therapeutics plans to share additional results in the first quarter of 2025 and engage with potential pharmaceutical partners and medical experts to determine the optimal next steps in belapectin's development. They are also analyzing data from patients who have completed 36 months of treatment.

Management Comments

• Dr. Khurram Jamil, Chief Medical Officer, stated they are highly encouraged by trends seen in the ITT population and the statistically significant reduction in new varices in the per-protocol population.
• Joel Lewis, Chief Executive Officer, expressed optimism about belapectin's potential and the unmet medical need for patients with MASH cirrhosis and portal hypertension.
• Dr. Naim Alkhouri, Chief Medical Officer and Director of the Steatotic Liver Program at Arizona Liver Health, is encouraged by the results and believes they warrant further clinical development.
• Dr. Naga Chalasani, David W. Crabb Professor of Gastroenterology and Hepatology, is pleased to see the results confirmed from previous trials and believes belapectin should continue in clinical development.

Industry Context

The results are relevant to the broader field of liver disease therapeutics, particularly for MASH-related cirrhosis, which currently has limited treatment options. The company is seeking to address a significant unmet medical need.

Comparison to Industry Standards

• The trial's design, with a large global patient population and a placebo control, aligns with industry standards for clinical trials.
• The use of a composite endpoint is common in liver disease trials, but the inclusion of intercurrent events may have introduced variability.
• The statistically significant result in the per-protocol population is a positive signal, but the lack of significance in the intent-to-treat population is a concern.
• Other companies developing treatments for MASH cirrhosis include Intercept Pharmaceuticals and Madrigal Pharmaceuticals, which have faced similar challenges in clinical trials.
• The 48.9% reduction in varices in the per-protocol population is a clinically meaningful result, but further data is needed to confirm its robustness.

Stakeholder Impact

• Shareholders may react negatively to the mixed results, potentially impacting the stock price.
• Patients with MASH cirrhosis may have hope for a new treatment option, but further development is needed.
• Employees may be impacted by the company's financial situation and future development plans.
• Potential partners may be cautious due to the mixed results.

Next Steps

• The company will continue to analyze the NAVIGATE trial data.
• Additional clinical updates will be provided in early 2025.
• The company will engage with potential pharmaceutical partners and medical experts to determine the next steps for belapectin development.

Key Dates

Keywords

belapectin, MASH, cirrhosis, portal hypertension, esophageal varices, clinical trial, NAVIGATE, Galectin Therapeutics, liver disease, Fibroscan