Roche and Zealand Pharma’s experimental obesity drug, petrelintide, has failed to meet market expectations in a mid-stage clinical trial, as detailed results released Thursday show the drug produced less weight loss than anticipated. Petrelintide is an amylin analog developed for patients with obesity or those who are overweight.
In the Phase 2 ZUPREME-1 study, patients treated with petrelintide saw an average weight reduction of 10.7% at 42 weeks compared to 1.7% in the placebo group, amounting to a placebo-controlled weight loss of 9%. Despite minimal side effects and what was described as “placebo-like tolerability,” this outcome fell short of analyst projections.
“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.”
Analysts had expected at least a 12% placebo-controlled weight loss based on early data from Eli Lilly’s eloralintid, which demonstrated around 16% in its own Phase 2 trial. William Blair noted that while cross-trial comparisons can be complicated by differences in enrolled populations—such as Lilly’s higher proportion of women participants—the gap between results was significant.
“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. The analysis also pointed out a possible ceiling effect at higher doses of petrelintide, suggesting limited additional benefit from increased dosing.
“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.
While Roche and Zealand did not disclose specific data on ZUPREME-1’s primary efficacy endpoint at week 28, they reported that petrelintide met this target with “statistically significant and clinically meaningful” reductions in body weight.
Zealand CEO Adam Steensberg highlighted safety findings: “placebo-like tolerability.” In ZUPREME-1, dropout rates due to side effects were similar between groups—4.8% among those receiving high-dose petrelintide versus 4.9% with placebo—with most adverse events being mild gastrointestinal symptoms such as nausea and vomiting.
William Blair commented further: “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.”
Roche and Zealand intend to advance petrelintide into Phase 3 trials later this year and will present additional mid-stage data from another study (ZUPREME-2) in late 2026. Petrelintide is administered once weekly via subcutaneous injection and works by targeting amylin receptors—a mechanism aimed at lowering blood glucose levels and delaying gastric emptying.
The development partnership follows Roche’s $1.65 billion upfront investment announced last March—with potential milestone payments up to $3.6 billion—to co-develop and commercialize petrelintide alongside Zealand Pharma.
In recent years Roche has expanded its obesity drug pipeline through acquisitions such as Carmot Therapeutics (for $2.7 billion), adding assets like CT-388—a dual GLP-1/GIP agonist—which recently showed promising results with a reported placebo-adjusted weight loss of over 22% after nearly one year of treatment during Phase 2 testing. Roche plans future studies combining CT-388 with petrelintide beginning later this year.
