On the heels of disappointing low-dose data results, Zealand Pharma is back with separate findings for its GLP-1/GLP-2 receptor dual agonist that have emboldened the biotech to push the candidate into phase 2b development.
The Danish biotech’s investigational weight loss candidate, dubbed dapiglutide, was tied to a mean placebo-adjusted reduction of up to 8.3% in body weight in a phase 1b multiple ascending dose trial, according to a Sept. 9 release.
The trial, known as MAD, assessed dapiglutide among 54 people overweight or obese against placebo. Patients were split up across three dose cohorts receiving 13 once-weekly doses of up to 13 mg of dapiglutide or placebo, with rapid up-titration every second week. Lifestyle modifications, such as diet or exercise, were not included in the study.
The trial’s primary endpoint, as listed on ClinicalTrials.gov, is the incidence of treatment-emergent adverse events (TEAEs). The new findings show dapiglutide to be safe and well tolerated, according to Zealand Pharma, with gastrointestinal (GI) symptoms reported as the most common TEAEs. Two participants discontinued treatment due to GI system adverse events. Overall, the number of GI events observed was consistent with studies with a similar escalation design for other incretin-based therapies, according to Zealand Pharma.
Higher dosing regimens up to 26 mg over 28 weeks are currently being tested in part 2 of the trial, with topline results slated for the first half of next year.
“Preliminary data further support that dapiglutide possesses a differentiated profile based on its unique dual agonist effects which we expect to translate to a positive effect on inflammation,” Zealand’s Chief Medical Officer David Kendall, M.D., said in the release. “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 biotech also intends to examine dapiglutide’s potential in certain obesity-related comorbidities, according to the company.
Back in May, dapiglutide failed to impress in a phase 2 trial, mustering up to an average 4.3% reduction in weight loss when given in low doses. The 54-person study involved administering either 4 mg weekly subcutaneous doses of dapiglutide, a 6 mg dose or placebo over 12 weeks. Participants who received 4 mg saw an average weight loss of 2.9%, barely above the 2.2% seen in the placebo arm. The 6 mg group saw a slightly larger weight loss of 4.3%.
The results suggest that the 4 mg and 6 mg doses are at the “lower end of the therapeutic range,” according to Zealand.
At the time, the biotech pointed to the MAD study, noting the higher doses being investigated.
The biotech’s main focus centers around petrelintide, a long-acting amylin analog. After reporting phase 1b data that suggest petrelintide may provide GLP-1-like efficacy without the side effects, Zealand Pharma said it believes the candidate could be “the backbone of therapy for weight management.”