Zealand Pharma and Roche Advance Petrelintide to Phase 3 for Chronic Weight Management

Zealand Pharma and Roche announced plans to advance petrelintide, a long-acting amylin analog, into Phase 3 clinical trials for chronic weight management, with trial initiation expected in the second half of 2026.¹

The decision follows internal program endorsement based on encouraging Phase 2 data and reflects growing confidence in amylin-based mechanisms as an alternative or complement to GLP-1–based therapies. The Phase 3 program will evaluate efficacy, safety, and tolerability of once-weekly subcutaneous dosing in patients with overweight or obesity.²

Petrelintide mimics the hormone amylin, which regulates appetite and gastric emptying, offering a distinct mechanism compared with incretin-based therapies. This differentiation may become increasingly important as the obesity drug market expands and diversifies.

What did the Phase 2 trial reveal?

The advancement is supported by results from the ZUPREME-1 Phase 2 trial (NCT06662539), which evaluated petrelintide in individuals with overweight or obesity. In that study, patients receiving treatment achieved up to 10.7% mean weight loss at 42 weeks, compared with 1.7% for placebo, meeting the trial’s primary endpoint.³

Notably, petrelintide demonstrated what investigators described as “placebo-like tolerability,” with low rates of gastrointestinal adverse events and no treatment discontinuations due to vomiting at the highest dose levels.⁴

Earlier-stage data, including a Phase 1b multiple ascending dose study, found that petrelintide showed dose-dependent and clinically relevant reductions in both body weight and waist circumference, reinforcing the compound’s pharmacologic activity and supporting continued development. Women in the Phase 1b study also appeared to respond better, with a retained favorable tolerability profile.⁵

While weight loss outcomes appear somewhat lower than leading GLP-1–based therapies, analysts have pointed to tolerability and patient adherence as potential differentiators for long-term use.

How does petrelintide fit into the evolving obesity landscape?

The transition to Phase 3 underscores broader industry interest in next-generation obesity treatments that move beyond GLP-1 receptor agonists. Amylin analogs such as petrelintide may offer complementary benefits, including improved tolerability and potentially better preservation of lean body mass.

The collaboration between Zealand Pharma and Roche highlights the strategic importance of diversifying mechanisms in metabolic disease pipelines. As competition intensifies, differentiation may hinge not only on efficacy but also on patient experience and long-term adherence.

The companies entered into a global collaboration and license agreement in March 2025 worth up to $5.3 billion to co-develop and co-commercialize petrelintide for weight management and other indications. The agreement includes the development of combination products such as a fixed-dose combination of petrelintide and CT-388, Roche’s dual GLP-1/GIP receptor agonist.

Under terms of the deal, Roche paid Zealand Pharma $1.65 billion upfront, with the potential to receive up to an additional $5.3 billion in milestone payments and sales-based incentives. A total of $1.4 billion will be due at the time of closing, with $250 million due over the first two years of the deal. 2. Roche enters into an exclusive collaboration & licensing agreement with Zealand Pharma to co-develop and co-commercialize petrelintide as a potential foundational therapy for people with overweight and obesity. Roche. March 11, 2025. Accessed April 30, 2026. https://www.roche.com/media/releases/med-cor-2025-03-12

What are the implications for patients and future research?

If successful in Phase 3, petrelintide could expand treatment options for patients who are unable to tolerate or do not respond optimally to current therapies. The emphasis on tolerability may be particularly relevant for chronic conditions like obesity, where sustained treatment is often required.

The upcoming Phase 3 trials will be critical in determining whether mid-stage findings translate into clinically meaningful outcomes at scale. They will also help clarify petrelintide’s positioning—either as a standalone therapy or in combination with other metabolic agents.

References

1. Zealand Pharma and Roche to advance weight loss drug to phase 3. (2026 Apr 29). https://www.globenewswire.com/news-release/2026/04/29/3284133/0/en/zealand-pharma-and-roche-to-advance-petrelintide-an-amylin-analog-to-phase-3-trials-for-chronic-weight-management.html
   
2. Zealand Pharma and Roche to advance weight loss drug to phase 3. (2026 Apr 29). Investing.com https://www.investing.com/news/company-news/zealand-pharma-and-roche-to-advance-weight-loss-drug-to-phase-3-93CH-4646305
   
3. Kartal Allan, A. (2026 Mar 6). Roche and Zealand’s Phase II obesity trial divides analyst opinion. Clinical Trials Arena. https://www.clinicaltrialsarena.com/news/roche-zealand-pharma-petrelintide-phase-ii-obesity-results/
   
4. Roche announces positive Phase II results for petrelintide, an amylin analog developed for people living with overweight and obesity. (2026 Mar 4). Press release. Roche.
   https://www.roche.com/media/releases/med-cor-2026-03-05 
   
5. Hesse, D., Olsen, M. B., Griffin, J., et al. (2025 Jun 20).Effects of the Novel Long-Acting Amylin Analogue Petrelintide on Body Weight and Waist Circumference by Sex in a Phase 1 Trial. Diabetes. https://diabetesjournals.org/diabetes/article/74/Supplement_1/1773-P/159580/1773-P-Effects-of-the-Novel-Long-Acting-Amylin?utm_source=chatgpt.com
   
6. Zealand Pharma and Roche enter collaboration and license agreement to co-develop and co-commercialize petrelintide as a future foundational therapy for people with overweight and obesity. GlobeNewswire. March 12, 2025. Accessed April 30, 2026. https://www.globenewswire.com/news-release/2025/03/12/3041113/0/en/Zealand-Pharma-and-Roche-enter-collaboration-and-license-agreement-to-co-develop-and-co-commercialize-petrelintide-as-a-future-foundational-therapy-for-people-with-overweight-and-o.html
   
7. Roche enters into an exclusive collaboration & licensing agreement with Zealand Pharma to co-develop and co-commercialize petrelintide as a potential foundational therapy for people with overweight and obesity. Roche. March 11, 2025. Accessed April 30, 2026. https://www.roche.com/media/releases/med-cor-2025-03-12