Zealand Pharma submits Marketing Authorization Application to the European Medicines Agency for glepaglutide in short bowel syndrome

Zealand Pharma (ZEAL) has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for glepaglutide, a long-acting GLP-2 analog, for treating adult patients with short bowel syndrome (SBS). The submission is based on positive Phase 3 trial results showing a statistically significant reduction in the need for parenteral support compared to placebo (5.13 liters/week vs 2.85 liters/week, p=0.0039) with twice-weekly dosing. Zealand plans to initiate a Phase 3 trial (EASE-5) in the second half of 2025 to support a U.S. regulatory submission.

Analysis

Zealand Pharma has achieved a significant regulatory milestone by submitting a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for glepaglutide, its long-acting GLP-2 analog for treating adult patients with short bowel syndrome (SBS). This submission is strongly supported by the pivotal Phase 3 EASE-1 trial, where twice-weekly administration of glepaglutide demonstrated a statistically significant reduction in weekly parenteral support volume by 5.13 liters, compared to a 2.85 liters reduction for the placebo group (p=0.0039). Notably, 14% of patients receiving glepaglutide twice weekly achieved complete enteral autonomy, discontinuing parenteral support, versus none in the placebo arm. While the once-weekly dosing regimen did not meet statistical significance for the primary endpoint in EASE-1, interim results from ongoing long-term extension trials (EASE-2 and EASE-3) and a mechanistic trial (EASE-4) provide further positive evidence. The company's outlook includes initiating the EASE-5 Phase 3 trial in the second half of 2025 to gather confirmatory data for a U.S. regulatory submission, where glepaglutide already holds orphan drug designation. This positions glepaglutide as a potential best-in-class therapy offering a more convenient twice-weekly dosing schedule compared to current daily treatments, potentially reducing patient burden significantly.

Key Decisions for Investors

• Investors should view the EMA submission as a key de-risking event for glepaglutide in the European market, with potential for future revenue generation upon approval.
• Closely monitor the initiation and progress of the EASE-5 trial in H2 2025, as successful outcomes are critical for accessing the U.S. market and realizing glepaglutide's full commercial potential.
• Consider the strong clinical data for the twice-weekly regimen, which could offer a competitive advantage in the SBS market, but also note that the once-weekly regimen did not meet its primary endpoint in EASE-1, requiring further evaluation.
• Acknowledge the positive sentiment and market impact signals, but remain cognizant of the inherent clinical development and regulatory approval risks typical of biotechnology investments, particularly pending EMA review and future U.S. FDA processes.