Zealand Pharma’s shares fell 32% in early morning trading Friday after its Roche-partnered asset petrelintide failed to meet investor expectations in a mid-stage clinical trial.
Yet another potential weight loss competitor has fallen short of defending champion Eli Lilly’s rival candidate in the clinic.
Roche and Zealand Pharma’s amylin analog obesity injection lowered body weight by more than 10% in a mid-stage study, with minimal side effects reported, but the results fell well short of analyst expectations, sending the biotech’s shares down 32% to $247.80 in premarket trading on Friday morning.
“We believe Zealand achieved the goal of demonstrating highly encouraging tolerability for petrelintide, though the magnitude of weight loss disappointed,” William Blair analysts wrote on Friday morning. “Therefore, we believe the real-world use-case for petrelintide will likely be materially reduced given the hypercompetitive nature of the obesity market.”
The results come from the Phase 2 ZUPREME-1 study, released Thursday, which included patients with obesity or who are overweight. Petrelintide elicited 9% placebo-controlled weight loss—10.7% mean weight reduction at 42 weeks in treated patients, as opposed to 1.7% in placebo comparators.
Investors had been expecting placebo-controlled weight loss of at least 12% for the study, according to William Blair. This efficacy was based on the early performance of Eli Lilly’s rival pipeline asset eloralintid, which achieved about 16% placebo-controlled weight loss in a Phase 2 trial. The analysts noted that cross-trial comparisons are fraught—particularly since Lilly’s trial may have enrolled more women, who tend to have higher weight loss. But the difference in the magnitude of weight loss between the trials is too large to ignore.
“We believe the difference in weight loss of 9.0% for petrelintide versus 16% for eloralintide is too large to attribute to the enrolled population alone,” William Blair wrote. Zealand’s drug also appeared to have a ceiling effect with the highest dose, so there may be a limit to how much more weight loss can be achieved with the drug.
“It is our view that this dynamic creates a challenging situation for petrelintide for which its tolerability profile supports higher dosing, but increasing the dose would be unlikely to lead to additional weight loss,” William Blair said.
Roche and Zealand’s announcement did not reveal specific 28-week weight-loss data, ZUPREME-1’s primary efficacy endpoint, noting only that petrelintide aced this bar and induced “statistically significant and clinically meaningful” decreases in body weight.
Where petrelintide might compete is in safety, with what Zealand CEO Adam Steensberg called “placebo-like tolerability.” In ZUPREME-1, 4.8% of patients in the highest petrelintide dose arm dropped out of the study due to side effects, as compared with 4.9% in the placebo group. Toxicities were mostly gastrointestinal-related, including nausea and vomiting, and the majority were mild.
William Blair said the tolerability profile was indeed a highlight of the data but still may not be enough to help Roche and Zealand rise in the cutthroat weight loss arena.
“Taken together, while we await detailed results of ZUPREME-1, our current view on petrelintide is that it will likely be used primarily in the maintenance setting, which demands a therapeutic intervention that exhibits placebo-like tolerability for chronic use,” the firm wrote.
Roche and Zealand plan to push petrelintide into Phase 3 later this year, David Kendall, Zealand’s chief medical officer, said in a statement. The partners will also present data from another mid-stage study, dubbed ZUPREME-2, in the second half of 2026.
Designed as a once-weekly subcutaneous injection, petrelintide is a long-acting peptide therapy that targets the amylin receptor, in turn helping to lower blood glucose levels and delaying gastric emptying. In March 2025, this mechanism attracted a $1.65 billion upfront investment from Roche, which promised up to $3.6 billion more in milestones to co-develop and co-commercialize the drug.
Roche made the investment in an effort to catch up to market leaders Eli Lilly and Novo Nordisk. The Swiss pharma also acquired a pipeline of GLP-1 and GIP drugs in the $2.7 billion acquisition of Carmot Therapeutics in December 2023. One of these assets, a dual GLP-1/GIP agonist drug called CT-388, cleared Phase 2 testing in January, with weekly injections eliciting a 22.5% placebo-adjusted weight loss at 48 weeks.
Roche is looking to study CT-388 in combination with petrelintide, with a trial set to start in the first half of this year.