Zealand Pharma's GLP-1/GLP-2 agonist shows 8.3% weight loss after earlier data setback

In light of recent developments, Zealand Pharma has revealed promising findings for its dual GLP-1/GLP-2 receptor agonist, dapiglutide, boosting the company's confidence to advance the candidate into phase 2b trials. The Danish biotech's investigational weight loss drug demonstrated a placebo-adjusted mean reduction in body weight of up to 8.3% in a phase 1b multiple ascending dose (MAD) trial, according to a September 9 announcement.

The MAD trial evaluated dapiglutide in 54 overweight or obese individuals, comparing the drug to a placebo. Participants were divided into three dose groups, receiving up to 13 mg of dapiglutide or placebo in 13 once-weekly doses, with dose escalation every two weeks. Importantly, the study did not incorporate lifestyle changes such as diet or exercise.

The primary endpoint of the trial, as reported on ClinicalTrials.gov, was the incidence of treatment-emergent adverse events (TEAEs). Zealand Pharma noted that dapiglutide was found to be safe and well tolerated. The most frequently reported TEAEs were gastrointestinal (GI) symptoms, which led to the discontinuation of treatment for two participants. The overall occurrence of GI events was consistent with other incretin-based therapies with similar escalation designs.

Currently, higher dosing regimens are being assessed in part 2 of the trial, with doses reaching up to 26 mg over 28 weeks. Topline results from this phase are expected in the first half of next year.

David Kendall, M.D., Zealand’s Chief Medical Officer, remarked on the preliminary data, highlighting dapiglutide's unique dual agonist effects, which may translate into positive impacts on inflammation. He stated, "Importantly, today’s exciting data give us the confidence needed to rapidly progress dapiglutide into a comprehensive phase 2b trial in people living with overweight and obesity planned for initiation in the first half of 2025." The company also plans to investigate dapiglutide's potential benefits in certain obesity-related comorbidities.

This announcement comes after dapiglutide's underwhelming performance in a previous phase 2 trial. In that study, the drug achieved a maximum average weight loss of 4.3% when administered in low doses. The trial, which included 54 participants, involved weekly subcutaneous doses of either 4 mg, 6 mg of dapiglutide, or a placebo for 12 weeks. The group receiving 4 mg experienced an average weight loss of 2.9%, barely surpassing the 2.2% seen in the placebo group. The 6 mg group observed a slightly higher weight loss of 4.3%, leading Zealand Pharma to consider these doses at the “lower end of the therapeutic range.”

At that time, Zealand Pharma pointed to the MAD study, which was investigating higher doses of dapiglutide.

Meanwhile, Zealand Pharma's primary focus remains on petrelintide, a long-acting amylin analog. The company has reported phase 1b data suggesting that petrelintide may offer GLP-1-like efficacy without the associated side effects. Zealand Pharma believes that petrelintide could become a fundamental therapy for weight management.