Zealand Pharma A/S has announced the enrollment of the first participant in its Phase 2b clinical trial, ZUPREME-1, evaluating petrelintide for the treatment of obesity and overweight with related co-morbidities. This multinational, multicenter trial marks a significant step in the development of a potential best-in-class alternative to incretin-based therapies.
The ZUPREME-1 trial (NCT06662539) is a randomized, double-blind, placebo-controlled study designed to assess the efficacy, safety, and tolerability of once-weekly subcutaneous injections of petrelintide, a long-acting amylin analog. The trial will compare five different doses of petrelintide against a placebo, in conjunction with a reduced-calorie diet and increased physical activity.
Trial Design and Endpoints
The ZUPREME-1 trial includes a screening period, a 16-week dose escalation period, a maintenance period up to week 42, and a follow-up period until week 51. The trial aims to enroll 480 participants across 33 sites in the United States, Poland, and Romania, with recruitment limited to a maximum of 60% of either male or female participants to ensure gender balance.
The primary endpoint of the trial is the percentage change in body weight from baseline to week 28. Secondary endpoints include percentage change in body weight from baseline to week 42, changes in waist circumference, HbA1c levels, high-sensitivity C-reactive protein (hsCRP), fasting lipids, and fasting glucose. Exploratory endpoints include changes in body composition at week 42, measured by Magnetic Resonance Imaging (MRI).
Petrelintide: A Novel Amylin Analog
Petrelintide (ZP8396) is designed for once-weekly subcutaneous administration, exhibiting chemical and physical stability at neutral pH to minimize fibrillation and allow for co-formulation with other peptides. As an amylin analog, petrelintide mimics the effects of endogenous amylin, a hormone co-secreted with insulin from pancreatic beta cells in response to nutrient intake.
Preclinical and clinical data suggest that petrelintide has the potential to deliver weight loss comparable to GLP-1 receptor agonists, but with improved tolerability and preservation of lean mass. In a statement, David Kendall, MD, Chief Medical Officer at Zealand Pharma, expressed enthusiasm for petrelintide's potential as a foundational therapy for weight management.
Expanding the Development Program
Zealand Pharma is planning to initiate a second Phase 2b trial in the first half of 2025, focusing on overweight or obese individuals with type 2 diabetes. This expansion of the development program underscores the company's commitment to exploring the full potential of petrelintide in addressing metabolic disorders.
Detailed results from a Phase 1b multiple ascending dose (MAD) trial of petrelintide were presented at the Obesity Society Annual Meeting (ObesityWeek) in November 2024.
