Zealand Pharma announces positive Phase 2 results for petrelintide, an amylin analog with potential to redefine the weight management experience for people living with overweight and obesity
Company announcement – No. 3 / 2026
Zealand Pharma announces positive Phase 2 results for petrelintide, an amylin analog with potential to redefine the weight management experience for people living with overweight and obesity
- Petrelintide achieved up to 10.7% mean body weight reduction at week 42 (versus 1.7% with placebo) and demonstrated placebo-like tolerability
- At the maximally effective dose, there were no cases of vomiting and no treatment discontinuations due to gastrointestinal adverse events
- The data reinforce further development of petrelintide in chronic weight management as monotherapy and as a combination partner
- Zealand Pharma will host a conference call today at 8:30 PM CET / 2:30 PM ET
Copenhagen, Denmark, March 5, 2026 – Zealand Pharma A/S (NASDAQ:ZEAL) (CVR-no. 20045078), a biotechnology company transforming the future of metabolic health, today announced positive topline results from the Phase 2 ZUPREME-1 dose-finding trial evaluating investigational petrelintide versus placebo in 493 people living with overweight and obesity (mean baseline BMI of 37 kg/m2; 53% females) for effects on body weight, safety, and tolerability. The trial met its primary endpoint, demonstrating that once-weekly subcutaneous injections of petrelintide (dose-escalated every fourth week) resulted in statistically significant and clinically meaningful reductions in body weight from baseline after 28 weeks in all five treatment arms compared to placebo.
Body weight reduction was sustained through week 42, with participants achieving up to 10.7% mean reduction from baseline using the efficacy estimand, compared to 1.7% with placebo (p-value <0.001). In the petrelintide treatment arm that achieved the greatest body weight reduction, 98% of trial participants successfully escalated to the targeted maintenance dose, underscoring strong adherence to dose escalation and a highly tolerable treatment approach. Accordingly, body weight reduction using the treatment regimen estimand was largely consistent with the efficacy estimand. Notably, female participants lost considerably more weight than male participants in this trial.
Adam Steensberg, President and Chief Executive Officer, of Zealand Pharma, said,
"Petrelintide has the potential to redefine weight management. Its placebo-like tolerability exceeds our expectations and, combined with double-digit weight reduction, sets a new standard. Key to unlocking the value of the obesity market and delivering improved health outcomes is a treatment patients can stay on. These results bring us closer to giving people the obesity treatments that fit the lives they actually want to live."
Petrelintide demonstrated a favorable tolerability profile comparable to placebo. The treatment discontinuation rate due to adverse events (AEs) was 4.8% with petrelintide in the maximally effective treatment arm versus 4.9% with placebo. The most frequently reported AEs were gastrointestinal-related, the vast majority of which were mild. The proportion of participants across all petrelintide treatment arms who experienced vomiting was lower than that observed with placebo, with no vomiting in the maximally effective dose arm, whereas the rates of diarrhea and constipation were consistent with those seen with placebo and remained in the single-digit range. Nausea was less common than in the prior 16-week Phase 1b trial of petrelintide, which used dose escalation every second week, and the vast majority was mild. Almost no events of nausea were reported after participants reached their targeted maintenance dose of petrelintide.
No unexpected safety signals were observed with petrelintide treatment, including for alopecia, fatigue, and neuropsychiatric adverse events (e.g., headache and depression). The proportion of petrelintide-treated participants experiencing injection site reactions was very low and consistent with placebo. Trial withdrawal due to any reason was 8.4% across petrelintide treatment arms compared to 13.6% with placebo.
David Kendall, MD, Chief Medical Officer of Zealand Pharma, said,
"We are very excited with the results of this Phase 2 trial of petrelintide, demonstrating double-digit body weight reduction with an exceptional tolerability profile and rates of GI adverse events comparable to placebo. These data reinforce petrelintide's potential to establish a new class of therapy and redefine the weight management experience for people living with overweight and obesity. We now look forward to rapidly advancing the program towards expected Phase 3 initiation later this year."
The final trial results, including a nine-week safety follow-up period, are expected to be presented at an upcoming scientific conference in 2026. The ZUPREME-1 data will inform the optimal Phase 3 designs and settings to evaluate petrelintide. Topline results from the second Phase 2 trial with petrelintide monotherapy, ZUPREME-2, which is evaluating petrelintide versus placebo in people living with overweight or obesity and type 2 diabetes, are expected in the second half of 2026 as well. A Phase 2 trial exploring the combination of petrelintide and CT-388 will be initiated in the first half of 2026.
In 2025, Roche and Zealand Pharma entered into an exclusive collaboration and licensing agreement to co-develop and co-commercialise petrelintide for people living with overweight and obesity.
About ZUPREME-1
ZUPREME-1 is a randomized, double-blind, placebo-controlled, parallel-group, multinational, multicenter, dose-finding, Phase 2 clinical trial (ClinicalTrials.gov ID: NCT06662539). The trial compares five doses of once-weekly petrelintide with placebo, when added to a reduced-calorie diet and increased physical activity in people with obesity or overweight with weight-related comorbidities.
The trial includes a screening period, a dose escalation period up to 16 weeks with dose escalation every fourth week, followed by a maintenance period until week 42, and a follow-up period after treatment is completed until week 51. ZUPREME-1 has enrolled more than 480 participants across 33 sites in the United States, Poland, and Romania.
The primary endpoint in the trial is the percentage change in body weight from baseline to week 28. Secondary endpoints include, but are not limited to, percentage change in body weight from baseline to week 42, change in waist circumference, change in hemoglobin A1c (HbA1c), change in high-sensitivity C-reactive protein (hsCRP), change in fasting lipids, and change in fasting glucose. Change in body composition at week 42 measured by Magnetic Resonance Imaging (MRI) is included as an exploratory endpoint in the trial.
About petrelintide
Petrelintide is a long-acting amylin analog suitable for once-weekly subcutaneous administration that has been designed with chemical and physical stability with no fibrillation around neutral pH, allowing for co-formulation and co-administration with other peptides1. Amylin is produced in the pancreatic beta cells and co-secreted with insulin in response to ingested nutrients. Amylin receptor activation has been shown to reduce body weight by restoring sensitivity to the satiety hormone leptin2,3, inducing a sense of feeling full faster. Current clinical data suggest a potential of petrelintide to deliver weight loss comparable to GLP-1 receptor agonists but with improved tolerability for a better weight management experience.
Conference call and webcast information
Zealand will host a conference call today, March 5 at 8:30 PM CET / 2:30 PM ET to discuss the topline results. Participating in the call will be Chief Executive Officer, Adam Steensberg; Chief Medical Officer, David Kendall; and Chief Financial Officer, Henriette Wennicke. The conference call will be conducted in English.
The live listen-only audio webcast of the call and accompanying slide presentation will be accessible at https://edge.media-server.com/mmc/p/6h89njh3. To receive telephone dial-in information and a unique personal access PIN, please register at https://register-conf.media-server.com/register/BIbc959bbf681c4a36b6e1b88c2618797a. Participants are advised to register for the call or webcast approximately 10 minutes before the start. A recording of the event will be available following the call on the Investor section of Zealand's website at https://www.zealandpharma.com/investors/events-presentations/.
About Zealand Pharma A/S
Zealand Pharma A/S (NASDAQ:ZEAL) is a biotechnology company focused on advancing medicines for obesity and metabolic health. Combining more than 25 years of peptide R&D expertise with a proprietary data platform that leverages advanced data‑driven and AI/ML approaches, Zealand Pharma aims to lead a new era in obesity and metabolic health.
To date, more than 10 Zealand Pharma‑invented drug candidates have entered clinical development, of which two products have reached the market and three candidates are in late-stage development. The Company has collaborations with global pharmaceutical and biotechnology partners for research, development, and commercialization.
Founded in 1998, Zealand Pharma is headquartered in Copenhagen, Denmark, with a U.S. presence in Boston, Massachusetts. Learn more at www.zealandpharma.com.
Forward-looking statements
This press release contains "forward-looking statements", as that term is defined in the Private Securities Litigation Reform Act of 1995 in the United States, as amended, even though no longer listed in the United States this is used as a definition to provide Zealand Pharma's expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products, the timing of the company's pre-clinical and clinical trials and the reporting of data therefrom and the company's significant events and potential catalysts in 2026 and financial guidance for 2026. These forward-looking statements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "goal," "intend," "may," "plan," "possible," "potential," "will," "would" and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented. The reader is cautioned not to rely on these forward-looking statements. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions, which may cause actual results to differ materially from expectations set forth herein and may cause any or all of such forward-looking statements to be incorrect, and which include, but are not limited to, unexpected costs or delays in clinical trials and other development activities due to adverse safety events, patient recruitment or otherwise; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; our ability to successfully market both new and existing products; changes in reimbursement rules and governmental laws and related interpretation thereof; government-mandated or market-driven price decreases for our products; introduction of competing products; production problems at third party manufacturers; dependency on third parties, for instance contract research or development organizations; unexpected growth in costs and expenses; our ability to affect the strategic reorganization of our businesses in the manner planned; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies, or may reject, fail to approve or may delay approval of our drug candidates or expansion of product labeling; failure to obtain regulatory approvals in other jurisdictions; exposure to product liability and other claims; interest rate and currency exchange rate fluctuations; unexpected contract breaches or terminations; inflationary pressures on the global economy; and political and geopolitical uncertainty. If any or all of such forward-looking statements prove to be incorrect, our actual results could differ materially and adversely from those anticipated or implied by such statements. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. All such forward-looking statements speak only as of the date of this company announcement and are based on information available to Zealand Pharma as of the date of this announcement. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.
Contacts
Adam Lange (Investors)
Vice President, Investor Relations
Zealand Pharma
[email protected]
Neshat Ahmadi (Investors)
Investor Relations Manager
Zealand Pharma
[email protected]
Rachel James-Owens (Media)
Vice President, Corporate Communications and Media Relations
Zealand Pharma
[email protected]
Amber Fennell, Jessica Hodgson, Sean Leous (Media)
ICR Healthcare[email protected]
+44 (0) 7739 658 783
Sources
1. Eriksson et al. Presentation at ObesityWeek, November 1–4, 2022, San Diego, CA. Link: https://www.zealandpharma.com/media/0gnfxg4b/zp8396-sema-coformulation-obesityweek-2022.pdf.
2. Mathiesen et al. Eur J Endocrinol 2022;186(6):R93–R111.
3. Roth et al. Proc Natl Acad Sci U S A 2008;105(20):7257–7262.
