Zealand Highlights Phase I Results for GLP-1, GLP-2 Candidate Despite Modest Weight Loss

Zealand Pharma, a Denmark-based company, released results from its latest Phase I trial for its GLP-1/GLP-2 candidate dapiglutide, designed to treat obesity. The findings indicated modest weight loss effects at lower doses. The DREAM trial’s topline data, which assessed the impact of low doses of dapiglutide over a 12-week period, revealed that a 4 mg dose led to an average weight loss of 2.9% from the baseline. This was only slightly better than the 2.2% average weight loss in the placebo group, resulting in a p-value of 0.483, which is not statistically significant.

A higher 6 mg dose of dapiglutide demonstrated a more favorable outcome, with an average weight loss of 4.3%, achieving a p-value of 0.077 compared to placebo. Notably, the trial did not incorporate lifestyle interventions such as diet or exercise. According to Zealand Pharma, the treatment was generally safe and well-tolerated, with nausea and decreased appetite being the most frequently reported side effects. The overall number of adverse events was lower than those seen with other incretin-based therapies, and there were no discontinuations among the participants.

The company plans to present more detailed results at an upcoming scientific conference and anticipates topline data from a Phase Ib trial in the latter half of 2024. David Kendall, Zealand’s Chief Medical Officer, expressed optimism about the body weight reductions observed. He remarked that these outcomes are consistent with those seen with shorter-term treatments using lower doses of other incretin-based therapies. Kendall also highlighted that the ongoing 13-week Phase Ib dose-titration trial is testing higher doses of dapiglutide, up to 13 mg, and that the company is exploring the potential for even higher doses based on the tolerability observed so far.

Despite the reported findings, investor reaction was negative, causing Zealand’s stock to decline significantly. Nevertheless, analysts from Jefferies provided a more nuanced view. They noted that while the results might seem "underwhelming" at first glance, the trial primarily served as a "mechanistic study" evaluating low doses. They emphasized that additional results are expected later in the year, which may provide a clearer picture of dapiglutide's potential. Jefferies analysts also mentioned that Zealand believes the drug could achieve weight loss of 20% or more, with the added GLP-2 activity potentially reducing systemic and gastrointestinal inflammation, thereby offering greater improvements in cardiometabolic health.

Meanwhile, other companies are also vying for a stake in the burgeoning weight loss market. For instance, Roche’s Genentech recently announced that its candidate, CT-388, part of a $2.7 billion acquisition of Carmot, achieved an 18.8% reduction in body weight in a Phase I trial. Additionally, SixPeaks Bio has surfaced with its own weight loss candidates, alongside an option for AstraZeneca to acquire the startup.

Currently, Eli Lilly and Novo Nordisk remain dominant in the weight loss domain. Notably, two recent studies highlighted that Novo’s semaglutide can maintain weight loss for up to four years, underscoring its strong position in the market.