Zealand Pharma’s investigational amylin analog, petrelintide, partnered with Roche, demonstrated significant weight loss and a tolerable safety profile in a Phase 2 obesity trial, according to a company announcement on March 5. Participants experienced up to 10.7% mean weight reduction at 42 weeks, while the treatment was associated with side effects comparable to placebo.
The trial, Zupreme-1, enrolled 493 adults who were overweight or living with obesity. Participants received once-weekly injections of petrelintide alongside a reduced-calorie diet and increased physical activity. Doses were escalated every four weeks to identify the optimal therapeutic level.
The study met its primary endpoint, showing statistically significant weight reductions across all five treatment arms compared with placebo after 28 weeks. While Zealand did not report specific weight-loss figures for the 28-week mark, the company confirmed that weight reduction was sustained through 42 weeks. By contrast, placebo participants lost an average of only 1.7% of body weight. Female participants reportedly experienced greater weight loss than male participants.
Petrelintide’s safety profile was favorable, with a 4.8% discontinuation rate due to adverse events—nearly identical to the 4.9% observed in the placebo group. Gastrointestinal events were the most commonly reported side effects, though most were mild, and no participants discontinued at the maximally effective dose due to vomiting or gastrointestinal issues. The drug also showed no unexpected safety signals, including alopecia, fatigue, headache, or depression.
Zealand emphasized that petrelintide could become a treatment option for patients who cannot tolerate GLP-1 medications while still seeking sustained weight loss. CEO Adam Steensberg, M.D., stated, “Petrelintide has the potential to redefine weight management. Its placebo-like tolerability exceeds our expectations and, combined with double-digit weight reduction, sets a new standard.”
The company plans to present additional trial results, including a nine-week safety follow-up, at an upcoming scientific conference later this year.
Roche invested $1.65 billion upfront last year to co-develop and co-commercialize petrelintide with Zealand, with the potential for up to $3.6 billion in milestone payments. Phase 3 trial designs are already being planned based on the Zupreme-1 study. Additionally, Zupreme-2, a second midstage trial assessing petrelintide in overweight or obese participants, including those with Type 2 diabetes, is expected to report top-line results in the second half of this year.
Another Phase 2 trial evaluating a combination of petrelintide and Roche’s dual GLP-1/GIP receptor agonist CT-388 is also scheduled to launch this year, highlighting Zealand and Roche’s continued expansion of obesity-focused therapeutics.
