Zealand Pharma Reports Positive 13-Week Phase 1b Trial Results for Dapiglutide

Zealand Pharma has revealed promising topline results from its 13-week Phase 1b multiple ascending dose clinical trial of the dual GLP-1/GLP-2 receptor agonist, dapiglutide. This investigational drug aims to manage weight by leveraging the benefits of both GLP-1 and GLP-2 agonists.

The trial demonstrated that dapiglutide led to a meaningful reduction in body weight, with participants experiencing up to an 8.3% decrease, adjusted for placebo, after 13 weekly doses. The medication was found to be safe and well-tolerated, with gastrointestinal side effects typical of incretin-based therapies. Higher doses, up to 26 mg over 28 weeks, are being explored in the ongoing Part 2 of the trial, with results anticipated in the first half of 2025.

"Our short-term trial data indicates significant weight reduction," stated David Kendall, MD, Chief Medical Officer of Zealand Pharma. He emphasized the drug's potential due to its unique dual agonist effects, which could also positively impact inflammation. The company is now assessing higher doses over a longer period and plans to initiate a Phase 2b trial for overweight and obese individuals in early 2025.

The first part of the Phase 1b trial involved 54 participants, mostly male, with a median age of 46 and a median baseline BMI of 30.0 kg/m2. These participants were randomly assigned to receive either dapiglutide or a placebo. By week 13, those on dapiglutide experienced a mean weight loss of 6.2%, while those on the placebo saw a mean weight gain of 2.1%.

Dapiglutide showed a favorable safety profile, with no severe treatment-emergent adverse events and only one serious adverse event unrelated to the drug. The most common side effects were gastrointestinal issues such as nausea and vomiting, consistent with other incretin-based therapies. Only two participants discontinued the treatment due to moderate gastrointestinal side effects. Injection site reactions were mild and anti-drug antibodies were noted in 14.3% of the participants.

In Part 2 of the trial, 30 participants are receiving up to 26 mg of dapiglutide over 28 weeks, with dosing adjustments every fourth week. Zealand Pharma aims to share topline results from this phase in the first half of 2025 and will present additional data from both parts of the trial at an upcoming scientific conference. The company is also planning a Phase 2b trial for people with overweight and obesity, starting in the first half of 2025. Furthermore, they intend to explore dapiglutide's potential in treating comorbidities related to obesity.

The Phase 1b trial is a randomized, double-blind, placebo-controlled study, investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of dapiglutide administered via subcutaneous injections. The trial does not include lifestyle modifications such as diet or exercise. Part 1 included rapid dose escalation every second week while Part 2 involves up-titration every fourth week.

Dapiglutide is a novel, long-acting dual GLP-1/GLP-2 receptor agonist designed to promote weight loss and mitigate low-grade inflammation by improving intestinal barrier function. Previous studies in healthy volunteers indicated significant weight loss and favorable pharmacokinetics, supporting a once-weekly dosing schedule.

Obesity, a chronic condition associated with widespread morbidity and mortality, often triggers systemic inflammation through compromised intestinal barrier integrity. This inflammation can lead to various comorbidities, including cardiovascular and liver diseases, inflammatory bowel disease, and neuro-inflammation.

Zealand Pharma, established in 1998 and headquartered in Copenhagen, Denmark, focuses on peptide-based medicines. The company has successfully advanced over ten drug candidates into clinical development, with two reaching the market and three in late-stage development. Zealand Pharma collaborates with multiple pharmaceutical companies and maintains commercial partnerships for its marketed products.