Zealand Pharma (ZEAL) Study result summary

Study Overview and Objectives

• ZUPREME-1 was a randomized, double-blind, placebo-controlled, multinational Phase II trial evaluating Petrelintide, an amylin analog, for weight management in overweight and obese adults, with 493 participants balanced by gender and a mean BMI of 37.

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

• The trial included five maintenance doses with dose escalation every four weeks, a maintenance period to week 42, and a nine-week safety follow-up.

• Baseline characteristics: mean age 47, mean body weight 107 kg, 53% female.

• 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, and 98% in the most effective dose arm escalated to maintenance dose.

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

Safety and Tolerability

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

• 70% of participants at the maximally effective dose reported no GI AEs; vomiting was less frequent than placebo and absent at the maximally effective dose.

• Most nausea events were mild and rare after reaching maintenance dose.

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

• Injection site reactions were very low and comparable to placebo.