Phase III studies to investigate survodutide for people living with obesity and overweight, with and without diabetes, cardiovascular disease and chronic kidney disease

Press release – No. 12 / 2023

• SYNCHRONIZE-1 and SYNCHRONIZE-2 are global Phase III studies of survodutide (BI 456906) in people living with obesity and overweight without and with type 2 diabetes, respectively
• A third study, SYNCHRONIZE-CVOT, is a global, long-term cardiovascular safety study of survodutide in people living with obesity and overweight with cardiovascular disease, chronic kidney disease or with risk factors for cardiovascular disease
• The Phase III studies will soon open for recruitment and include a longer overall treatment period and a higher maximum dose for maintenance treatment compared with Phase 

Boehringer Ingelheim and Zealand Pharma A/S (NASDAQ: ZEAL) announced the initiation of three Phase III trials investigating survodutide (also known as BI 456906) for people living with overweight or obesity. The trial design builds upon learnings from Phase II, in which people living with overweight or obesity achieved up to 19 percent weight loss.1 The Phase III trials will soon open for recruitment.

Additional Phase II data, presented at the 59th Annual Meeting of the European Association for the Study of Diabetes (EASD), demonstrated reductions in absolute waist circumference (up to 16.0 cm), absolute body weight (up to 19.5 kg) and absolute systolic and diastolic blood pressure (up to 8.6 mmHg and 4.8 mmHg, respectively) over 46 weeks.2

“As the prevalence of the disease of obesity continues to increase,3 it is imperative that we develop additional innovative approaches to address this serious, chronic disease,” said Carel le Roux, M.D., Ph.D., Professor at University College in Dublin, Ireland, and Principal Investigator of the trial. “Survodutide has a novel mechanism of action with the potential to reduce appetite while increasing liver energy expenditure.4 The promising Phase II data give us reason to be hopeful about the potential of survodutide as a treatment for people living with the disease of obesity.4”

SYNCHRONIZE-1 (NCT06066515) and SYNCHRONIZE-2 (NCT06066528), now listed on clinicaltrials.gov, are Phase III studies investigating survodutide in people with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) with comorbidities, including dyslipidemia, hypertension and obstructive sleep apnea. SYNCHRONIZE-1 will enrol people without type 2 diabetes (A1C <6.5%) and SYNCHRONIZE-2 will enrol people with type 2 diabetes (A1C ≥6.5%, <10%). 

For both studies, the primary endpoints are percent change in body weight at week 76 and the proportion of people who achieve body weight loss of 5% or more at week 76. Secondary endpoints include body weight reductions of at least 10%, 15% and 20% at week 76. A total of 600 participants will be enroled in each of the two studies, randomized to receive weekly subcutaneous injections of either survodutide, reaching a maximum dose of 3.6 mg or 6.0 mg for maintenance treatment, or placebo.

The third study, SYNCHRONIZE-CVOT, is a Phase III trial that will enrol people with overweight or obesity with cardiovascular disease, chronic kidney disease, or risk factors for cardiovascular disease. In SYNCHRONIZE-CVOT, the primary endpoint is the time to first occurrence of any one of five major adverse cardiac events (5P-MACE): death, non-fatal stroke, non-fatal myocardial infarction, ischemia-related coronary revascularization and heart failure events.

“By implementing the valuable insights gained from the Phase II study, we are confident in the accelerated development of survodutide,” said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. “Obesity is a chronic disease associated with serious health complications that affects hundreds of millions worldwide.5 With these trial initiations, we continue to build on our heritage of bringing differentiated and innovative treatments to address cardiovascular, renal, and metabolic diseases.”

“We are excited that survodutide will shortly enter Phase III trials through the global SYNCHRONIZE program for people living with overweight or obesity,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “With novel peptide therapeutics like survodutide, we are targeting key metabolic pathways, and these therapies have the potential to address one of the most significant healthcare challenges in medicine today.”

About Overweight and Obesity

In 2016, more than 1.9 billion adults were overweight — defined as a body mass index (BMI) of 25 or more..5 Of these, over 650 million were living with obesity — defined as a BMI of 30 or more.3 The World Heart Federation predicts that by 2025, 2.7 billion adults could be living with overweight or obesity, making it a global health challenge and placing a high burden on individuals, healthcare systems, and society.3 Overweight and obesity are complex chronic conditions involving abnormal or excessive fat accumulation that presents a risk to a person’s overall health.6

About Survodutide (BI 456906)

Survodutide is a glucagon/GLP-1 receptor dual agonist that activates both the GLP-1 and glucagon receptors, which are critical to controlling metabolic functions.4 Co-invented by Boehringer Ingelheim and Zealand Pharma, survodutide is part of Boehringer Ingelheim’s research and development portfolio in the cardio-renal-metabolic disease areas. In addition to studies in obesity and overweight, survodutide is also being evaluated in a Phase II study in adults with NASH and liver fibrosis (stages F1/F2/F3).7 The trial is expected to complete in Q4 2023. Survodutide has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for adults with NASH.8

About Boehringer Ingelheim

Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at www.boehringer-ingelheim.com  

Boehringer Ingelheim’s Intended Audiences Notice

This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

About Zealand Pharma A/S 

Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products.

Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. that includes Boston. For more information about Zealand’s business and activities, please visit www.zealandpharma.com.

Forward-Looking Statement

The above information contains forward-looking statements that provide Zealand Pharma’s expectations or forecasts of future events. 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. 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. All such forward-looking statements speak only as of the date of this release and are based on information available to Zealand Pharma as of the date of this release.

Carel Le Roux, MBChB, Ph.D., serves on advisory boards and speaker panels for Boehringer Ingelheim, Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Currax, Zealand Pharma and Rhythm Pharma.

Media Contact

Anna Krassowska, PhD
Vice President, Investor Relations & Corporate Communications
Zealand Pharma
Email: ank@zealandpharma.com

Harro Ten Wolde
Head of Global Media Relations
Boehringer Ingelheim
Email:  harro.ten_wolde@boehringer-ingelheim.com

References

1 Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with survodutide (BI 456906). Available at https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/obesity/phase-ii-clinical-trial-weight-loss-results.

2 Carel Le Roux et al., European Association for the Study of Diabetes (EASD), 59th Annual Meeting 2023, Hamburg, Germany, October 3, 2023, OP 10 Activating two or three G´s; one of us is lonely, 3:15–4:45 pm

3 World Heart Federation. Obesity. 2015. Available at https://world-heart-federation.org/what-we-do/obesity/#:~:text=Global%20estimates%20suggest%20that%20almost,overweight%20or%20obesity%20by%202025. Accessed September 2023.

4 T. Zimmerman et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Molecular Metabolism. 2022;66:101633.

5 World Health Organization. Obesity and Overweight. Available at https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed September 2023.

6 Bray GA et al. Obesity: A chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev 2017;18:715–723.

7 ClinicalTrials.gov. A Study to Test Safety and Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3). Available at https://clinicaltrials.gov/ct2/show/NCT04771273. Accessed September 2023.

8 Boehringer Ingelheim and Zealand Pharma Receive FDA Fast Track Designation for Investigational Treatment for NASH. Available at https://www.boehringer-ingelheim.com/us/press-release/boehringer-ingelheim-and-zealand-pharma-receive-fda-fast-track-designation. Accessed September 2023.