Zealand Pharma (ZEAL) Study result summary

Study Overview and Objectives

• ZUPREME-1 was a randomized, double-blind, placebo-controlled, dose-finding Phase II trial evaluating Petrelintide, an amylin analog, for weight management in overweight and obese adults, with 493 participants balanced by gender and geography.

• The primary endpoint was percentage change in body weight at week 28; secondary endpoints included weight change at week 42, body composition, and cardiometabolic risk factors.

• Five maintenance doses of Petrelintide were compared to placebo, with dose escalation every four weeks.

• Baseline characteristics were balanced; mean age 47, mean BMI 37 kg/m², 53% female.

• The trial was conducted across 33 sites in the US, Poland, and Romania.

Key Efficacy Results

• Petrelintide achieved up to 10.7% mean weight loss at week 42 versus 1.7% for placebo, with sustained double-digit reductions and no plateau observed.

• All five treatment arms showed clinically meaningful weight loss at 28 weeks, meeting the primary endpoint.

• Female and European participants experienced greater weight loss than males and US participants.

• Nearly all participants on active treatment lost weight, with 98% in the most effective dose arm escalating to maintenance dose.

• Weight reduction was consistent across efficacy and treatment regimen estimands.

Safety and Tolerability

• Petrelintide demonstrated a placebo-like safety profile, with GI adverse event rates similar to placebo and a 4.8% discontinuation rate due to AEs, comparable to placebo (4.9%).

• About 70% of participants on the highest dose reported no GI adverse events; most nausea events were mild and rare after reaching maintenance dose.

• Vomiting was less frequent than placebo, and no vomiting occurred at the maximally effective dose.

• No unexpected safety signals were observed, including for alopecia, fatigue, or neuropsychiatric events.

• No differences in safety or tolerability were observed between men and women.