Zealand Pharma starts Phase 2b ZUPREME-2 trial for petrelintide in overweight type 2 diabetes patients

COPENHAGEN, Denmark, April 24, 2025 – Zealand Pharma A/S, a biotechnology enterprise listed on Nasdaq under the ticker ZEAL, has made a significant advancement in its quest to develop peptide-based therapeutic solutions. The company recently announced the commencement of a key clinical trial named ZUPREME-2. This Phase 2b study aims to investigate the efficacy and safety of petrelintide, a promising long-acting amylin analog, in individuals dealing with overweight or obesity and type 2 diabetes.

The trial is particularly notable for its focus on petrelintide, which offers an innovative approach to weight management and glycemic control. David Kendall, MD, the Chief Medical Officer at Zealand Pharma, highlighted the significance of this trial, referring to it as an essential component of the company’s clinical development strategy. He emphasized the potential of amylin agonism to induce substantial weight loss and improve blood sugar control, underscoring the potential of petrelintide to emerge as a superior alternative to existing incretin-based therapies.

ZUPREME-2 is designed as a robust, randomized, double-blind, placebo-controlled, parallel-group clinical trial across multiple centers. It will examine the effects of three different doses of petrelintide, administered weekly, in conjunction with a regimen of reduced-calorie intake and increased physical activity. The trial is structured to include a screening phase, a treatment phase spanning up to 16 weeks with dose adjustments every four weeks, a maintenance phase concluding at week 28, and a follow-up segment extending to week 38. The objective is to enroll around 200 participants to thoroughly assess the treatment’s impact.

The primary outcome measure for ZUPREME-2 is the percentage change in body weight from the start of the trial to the 28th week. Secondary outcomes incorporate a variety of metrics, such as achieving body weight reduction of 5% and 10%, alterations in waist circumference, and changes in levels of hemoglobin A1c, high-sensitivity C-reactive protein, fasting glucose, and fasting lipids.

Petrelintide itself represents a significant advancement in peptide-based treatments. It is designed for subcutaneous injection once a week and exhibits chemical stability without fibrillation at neutral pH, facilitating its combination with other peptide treatments. Amylin, the hormone upon which petrelintide is modeled, is naturally produced in the pancreatic beta cells and works alongside insulin to regulate nutrient-induced responses. The activation of amylin receptors has been shown to enhance the body's response to the satiety hormone leptin, promoting a quicker sensation of fullness and thereby contributing to weight loss.

Zealand Pharma has been actively presenting the capabilities of petrelintide, showcasing detailed results from a Phase 1b trial at the Obesity Society Annual Meeting in 2024. In addition to the ZUPREME-2 trial, petrelintide is undergoing evaluation in another trial, ZUPREME-1, which focuses on its effects over a longer period with varying doses.

In a strategic move to boost the development and commercialization of petrelintide, Zealand Pharma entered into a partnership with Roche earlier this year. This collaboration aims to co-develop petrelintide and leverage the strengths of both companies to position it as a foundational therapy for managing overweight and obesity. The agreement is currently pending regulatory approvals and is anticipated to be finalized by the second quarter of 2025.

Zealand Pharma, founded in 1998 and headquartered in Copenhagen, has developed a strong reputation in the biotechnology field, particularly in peptide-based medicine. It has successfully advanced over ten drug candidates into clinical development, with two already available in the market and several others in late-stage development. The company continues to foster partnerships with other pharmaceutical entities to expand its reach and impact in therapeutic solutions.