Zealand/Roche Kick Off Registrational Phase 3 ZUPREME Program for Petrelintide (~7,000 Participants)

Zealand/Roche Kick Off Registrational Phase 3 ZUPREME Program for Petrelintide (~7,000 Participants)

On September 22, 2026, Zealand Pharma announced the initiation of the registrational Phase 3 ZUPREME program for petrelintide, its once-weekly subcutaneous amylin analog co-developed with Roche — the first amylin-class monotherapy to reach registrational testing for chronic weight management, and a milestone in the "tolerability-first" challenge to the GLP-1 incumbents.

Program structure (Zealand press release, Sep 22, 2026): three placebo-controlled monotherapy trials expected to enroll ~7,000 participants in total —

• ZUPREME-3: ~3,900 participants, overweight/obesity without T2D;
• ZUPREME-4: ~600 participants, overweight/obesity with T2D;
• ZUPREME-5: ~2,500 participants, overweight/obesity with established cardiovascular disease. Primary endpoint in all three: percentage change in body weight from baseline to week 64.

The program builds on Phase 2 results showing "double-digit weight loss with a tolerability profile largely comparable to placebo¹" — petrelintide's core pitch is that amylin-class tolerability enables the long-term adherence chronic weight management requires. Zealand CMO David Kendall: "The Phase 3a program is designed to confirm the first-choice potential of petrelintide – supported by the data we have seen throughout the clinical trials with petrelintide: clinically meaningful double-digit weight reduction and a tolerability profile that supports the long-term adherence that chronic weight management requires."

A Phase 2 trial of petrelintide combined with Roche's GLP-1/GIP dual agonist enicepatide (CT-388) is planned for initiation in H2 2026 — the combination is where Roche/Zealand hope to compete on efficacy as well as tolerability.

Investor takeaway: This fires the Phase 3-initiation watch for petrelintide (the zenagamtide/amycretin half remains pending — Novo's version is now tracked separately). Amylin is the most crowded next-gen modality after GLP-1/GIP; readouts from these trials land in 2028-29, but the initiation itself validates Zealand's Phase 2 data package and puts the first pure-amylin registrational dataset on the board ahead of Novo's cagrilintide-franchise follow-ons. See Novo Strategic Reset Under Doustdar: Post-CMD Buying Spree Continues with $2.6B Hengrui Deal for Once-Weekly Obesity Pill for why Morningstar ranks amylin-class zenagamtide above CagriSema in Novo's own pipeline.