Zealand touts safety of new ‘double-G’ drug despite modest weight loss in small trial

Zealand Pharma appears to have taken a small step forward with a candidate that targets both GLP-1 and GLP-2, an approach that aims to ease side effects seen in many obesity drugs.

In the investigator-led, 54-subject DREAM trial, dapiglutide delivered a low 2.9% weight loss change from baseline in the 4 mg dose (p=0.483), but the 6 mg dose offered a relatively higher 4.3% change (p=0.077) compared with placebo (2.2%) at 12 weeks, the Danish biotech said Thursday.

While it’s tough to compare obesity drug data, for context: Novo Nordisk’s semaglutide can offer 6% weight loss at week 12 in large trials. Data for Eli Lilly’s tirzepatide showed it can deliver 6.9% weight loss at 12 weeks with lifestyle tweaks in a late-phase study. Meanwhile, Amgen’s buzzy MariTide has 12-week Phase 1 data clocking in at 14.5% weight loss. All three drugs target GLP-1, but tirzepatide is also a GIP receptor agonist and MariTide is a GIP receptor antagonist.

Zealand’s stock is down 4% on the Copenhagen stock exchange.

David Kendall

While Zealand’s numbers may appear “underwhelming,” the Phase 2a study was investigating low doses of dapiglutide, Jefferies analysts wrote in a Friday note. With the candidate’s “benign” safety profile so far, the new data support exploration in higher doses, they added. The rationale behind targeting GLP-2 is that it could improve tolerability to GLP-1 agonism.

“Our ongoing 13-week Phase 1b dose-titration trial is currently evaluating higher doses of dapiglutide up to 13 mg, and based on the tolerability profile observed to date, we will seek to investigate even higher doses going forward,” Zealand medical chief David Kendall said in a statement. Zealand is ultimately targeting more than or equal to 20% weight loss with dapiglutide.

In the Phase 2a, the most common treatment-emergent issues were related to the gastrointestinal system, such as nausea and reduced appetite, and there were no discontinuations. The overall number of events was also lower than other incretin-based approaches, according to the company.