Zealand's new obesity drug: Low dose tolerable, lacks efficacy

Zealand Pharma has provided an early look at its second obesity program, dapiglutide, suggesting that this GLP-1/GLP-2 receptor dual agonist may offer a safety advantage over its more advanced candidate, survodutide. However, determining the optimal dose that balances efficacy and tolerability will be crucial moving forward.

The company shared 12-week data from the DREAM trial, which included 54 participants with obesity. The trial investigated the effects of dapiglutide at doses of 4mg and 6mg. Results indicated a mean weight loss from baseline of 2.9% for the 4mg dose and 4.3% for the 6mg dose, compared to 2.2% for the placebo group. Although these weight-loss results did not reach statistical significance at the low doses tested, the company noted that no participants discontinued the study due to adverse events. Overall, the number of adverse events observed was lower than those reported in studies of other incretin-based therapies.

In contrast, data for Zealand's other obesity candidate, survodutide, a glucagon/GLP-1 receptor dual agonist being developed in partnership with Boehringer Ingelheim, showed different trends. Last year, Phase II results revealed that a 4.8mg dose of survodutide resulted in nearly 19% weight loss in patients with obesity after 46 weeks. However, nearly 25% of participants dropped out due to gastrointestinal adverse events. Despite these tolerability issues, the companies progressed survodutide to a Phase III trial in August.

Given the modest weight loss observed in the DREAM trial, Zealand Pharma's leadership emphasized that much higher doses of dapiglutide are currently being evaluated. A separate Phase Ib trial is underway, investigating 13mg doses over 13 weeks, with top-line results expected in the second half of the year. Chief Medical Officer David Kendall stated that, based on observed tolerability, even higher doses might be explored in future studies.

Overall, while dapiglutide has shown a promising safety profile at lower doses, its efficacy in producing significant weight loss remains to be proven at higher doses. Identifying the right dose will be key to advancing this candidate in the competitive obesity treatment landscape.