Zealand Pharma and Roche take petrelintide to Phase 3

Zealand Pharma and Roche have formally endorsed moving petrelintide, a long-acting amylin analog for chronic weight management, into Phase 3 testing, with the first pivotal trials planned to begin in the second half of 2026 ^[1]. The announcement, made April 29, 2026 from Zealand's Copenhagen headquarters, follows mid-stage results the companies say combine double-digit weight loss with tolerability close to placebo ^[1].

The Phase 3 program is designed to test petrelintide as a once-weekly injection under the skin in adults living with obesity, or with overweight plus weight-related health conditions, measuring efficacy, safety and tolerability ^[1]. "By delivering exceptional tolerability and desired weight loss without disrupting daily life, we aim to redefine the weight management experience for people living with overweight and obesity," said Adam Steensberg, Zealand's president and chief executive ^[1].

What the Phase 2 data showed

The decision rests on ZUPREME-1 (NCT06662539), a Phase 2 trial in people with overweight or obesity. Participants on petrelintide lost up to 10.7% of body weight on average at 42 weeks, compared with 1.7% for placebo, meeting the trial's main goal ^[2]. Investigators described the tolerability as "placebo-like," with low rates of gastrointestinal side effects and no treatment discontinuations due to vomiting at the highest dose levels ^[2].

An earlier Phase 1b multiple-ascending-dose study found dose-dependent drops in both body weight and waist size, and women appeared to respond better while still tolerating the drug well ^[2].

Petrelintide works differently from semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound). It mimics amylin, a hormone made in pancreatic beta cells and released along with insulin after eating ^[1]. Activating amylin receptors has been shown to lower body weight partly by restoring sensitivity to leptin, a satiety hormone, so people feel full sooner ^[1]. Amylin also influences how fast the stomach empties ^[2].

One trade-off is plain in the numbers. As BioPharm International noted, petrelintide's weight-loss results look somewhat lower than leading GLP-1-based therapies, and analysts have pointed to tolerability and staying on treatment as the potential differentiators instead ^[2]. For scale, a separate pipeline tracker lists retatrutide at 28.3% mean weight loss at 80 weeks in its TRIUMPH-1 pivotal trial and survodutide at 16.6% at 76 weeks in SYNCHRONIZE-1 — though those are longer trials of different drug classes, so the figures are not a head-to-head comparison ^[3].

The Roche partnership

Zealand and Roche signed a global collaboration and license agreement in March 2025 to co-develop and co-commercialize petrelintide ^[1][2]. Reported deal terms are described inconsistently in the source: it is characterized both as worth up to $5.3 billion overall and as $1.65 billion upfront with up to an additional $5.3 billion in milestones and sales incentives, with $1.4 billion due at closing and $250 million over the first two years ^[2].

The partners are also developing petrelintide in combination with enicepatide (CT-388), Roche's dual GLP-1/GIP receptor agonist. A Phase 2 trial of that combination was planned to start in the second quarter of 2026 ^[1].

Why it matters for patients

Nausea, vomiting and other stomach side effects are among the most common reasons people stop GLP-1 treatment. A drug that produces meaningful weight loss with fewer of those problems could matter for people who have struggled to stay on current medicines, and the companies are explicitly framing petrelintide as an option built around adherence over the long term ^[1][2]. If Phase 3 succeeds, petrelintide could widen choices for people who cannot tolerate or do not respond well to existing therapies ^[2].

But nothing changes today. Petrelintide is not approved anywhere, Phase 3 has not started, and mid-stage results do not always hold up in larger trials. The sources do not say how many people the Phase 3 program will enroll, what doses will be studied, how long the trials will run, when data will read out, or when a US filing might occur. Pricing and insurance coverage are also unknown.

What happens next

• Second quarter of 2026: planned start of the Phase 2 trial combining petrelintide with enicepatide (CT-388) ^[1].
• Second half of 2026: planned initiation of the Phase 3 chronic weight management program ^[1][2].

A pipeline tracker also lists CagriSema's US regulatory decision as expected through late 2026, with no FDA date publicly confirmed ^[3].