Zealand Pharma has shared primary endpoint data on Roche-partnered petrelintide, revealing that the middle dose of the amylin analog delivered the highest weight loss—9.8%—at Week 28.
Roche, which in 2025 paid $1.65 billion upfront for petrelintide, and Zealand shared topline results from the Zupreme 1 trial in March and presented an expanded dataset in June. In those updates, the partners focused on the up to 10.7% mean weight loss seen at Week 42 of the trial without disclosing the Week 28 primary endpoint analysis or digging into the results for each dose cohort.
Now, The Lancet Diabetes & Endocrinology has published a closer look at the phase 2 data. Weight loss at Week 28 was lowest on the bottom two doses, with the mean reduction in the 1 mg and 2.5 mg arms coming in at 7.9%. Mean weight loss stepped up to 9.8% on the 5 mg dose.
Beyond that, the primary endpoint data provide no support for further dose increases. Mean weight loss in the 7 mg and 9 mg cohorts was 9.3% and 9.4%, respectively. With weight loss on placebo hitting 1.7% at Week 28, the control-adjusted reduction peaked at 8.1% on the 5 mg dose.
All the data come from efficacy estimand analyses. Using the treatment policy estimand, which handles discontinuations differently, Zealand reported mean reductions in body weight from baseline to Week 42 of up to 10.2%, versus 1.4% for placebo.
Cross-trial comparisons suggest petrelintide’s efficacy is unlikely to lead the amylin field. Eli Lilly saw up to 11.3% weight loss at Week 12 of a phase 1 trial of its amylin receptor agonist, eloralintide, rising to up to 20.1% at Week 48 of a phase 2 study.
Roche and Zealand have touted tolerability as an area where petrelintide may have an edge. Nausea was more common on petrelintide than placebo, affecting 20% of participants compared to 6% in the control arm. Zealand also saw a higher rate of constipation on petrelintide, 7%, than on placebo, 4%. But rates of vomiting and diarrhea were the same or lower on petrelintide than on placebo.
The emerging risk-benefit profile of amylin agonists has spurred speculation that the molecules could be a first-line treatment for obesity, as BMO Capital Markets analysts explained in a June 6 note to investors.
“Given largely improved tolerability of these agents with modest to better efficacy, physicians made the case that a future treatment paradigm may prioritize amylin agents first with combo treatments reserved for patients who need higher efficacy or are refractory,” the analysts said.
Roche is scheduled to start three phase 3 studies of petrelintide Wednesday, according to the federal trials database. The trials target three populations: obesity or overweight; obesity or overweight plus Type 2 diabetes; and obesity or overweight plus cardiovascular disease. All the trials will test petrelintide as a monotherapy. The obesity and diabetes trials have primary completion dates in late 2028.
