Zealand Pharma reveals positive Phase 1b results for petrelintide trial

Zealand Pharma has revealed promising initial outcomes from their Phase 1b 16-week multiple ascending dose (MAD) clinical trial involving petrelintide, a long-acting amylin analog under development for weight management. The study demonstrated significant body weight reductions and confirmed the safety and tolerability of petrelintide across various dosages. Following these positive results, Zealand Pharma plans to commence a Phase 2b clinical trial in the second half of 2024.

Conducted over 16 weeks, the Phase 1b trial included 48 participants, predominantly male, with a median age of 49 years and a baseline BMI of 29 kg/m². Participants were randomly assigned to receive either petrelintide or a placebo, with the study structured into three dose cohorts. Those who received the high dose of petrelintide experienced a mean body weight reduction of 8.6%, compared to a 1.7% reduction for those on the placebo.

David Kendall, MD, Chief Medical Officer of Zealand Pharma, highlighted the significance of these results, noting that petrelintide exhibited both substantial weight reduction and a favorable tolerability profile. Kendall expressed optimism about the potential of petrelintide as an alternative to GLP-1 receptor agonists for managing overweight and obesity, suggesting that it could offer comparable weight loss benefits with a better patient experience.

The trial's assessment of petrelintide's safety and tolerability revealed no serious or severe adverse events. Mild gastrointestinal side effects were the most common, with only isolated instances of moderate nausea and vomiting. Injection site reactions were infrequent and mild, and no anti-drug antibodies were detected.

These preliminary findings will be elaborated upon once additional data, including post-treatment follow-up from the third cohort, is available. Zealand Pharma anticipates presenting detailed results at a scientific conference later this year. The company is poised to advance petrelintide's clinical development, with a Phase 2b trial set to begin later in 2024.

The MAD trial, conducted at a single center, is designed as a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of petrelintide. The trial consists of two parts: Part 1 involved 20 participants with a BMI range of 21.0–29.9 kg/m², who received six weekly doses of either 0.6 mg or 1.2 mg of petrelintide or a placebo. Part 2 included 48 participants with a BMI range of 27.0–39.9 kg/m², who received 16 weekly doses within three dose cohorts, exploring higher doses than those in Part 1. Participants in the higher dose cohorts were maintained on the maximum assigned dose for periods of eight and six weeks, respectively.

Petrelintide, also known as ZP8396, is engineered for once-weekly subcutaneous administration. It boasts chemical and physical stability at neutral pH, reducing fibrillation and permitting co-formulation with other peptides. This amylin analog, secreted alongside insulin by pancreatic beta cells, has shown potential in preclinical and clinical settings to achieve weight loss comparable to GLP-1 receptor agonists but with improved tolerability and preservation of lean mass.

In summary, Zealand Pharma's latest findings regarding petrelintide underscore its promise as a potent and well-tolerated treatment for weight management. The company's proactive steps toward further clinical trials highlight their commitment to developing innovative peptide-based medicines that address significant health challenges like obesity.