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)

Press Release­­­­­­­ No. 5 / 2023

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)¹

• Up to 40% of people who reached the highest two doses of survodutide (BI 456906) achieved a weight loss of at least 20%¹
• Survodutide has a novel mechanism of action (agonism of the dual GCG/GLP-1 receptors) that may have direct effects on energy expenditure in the liver in addition to decreasing appetite²
• Detailed data were presented at the 2023 American Diabetes Association’s 83^rd Scientific Sessions

Ingelheim, Germany, and Copenhagen, Denmark, 23 June, 2023 – Boehringer Ingelheim and Zealand Pharma A/S (Nasdaq: ZEAL) today announced additional data demonstrating superior efficacy with survodutide (also known as BI 456906) versus placebo in people with overweight or obesity without type 2 diabetes after 46 weeks of treatment.¹ The findings were presented at the 2023 American Diabetes Association’s 83^rd Scientific Sessions in San Diego, CA, U.S.

The Phase II study included two analyses: planned (assigned dose at randomization, which was also the primary endpoint) and actual (dose at the end of treatment).¹ People who completed the study on the 4.8 mg dose (actual treatment analysis) achieved nearly 19% weight loss.¹ As previously announced, the planned treatment analysis demonstrated nearly 15% weight loss for all those randomized to the 4.8 mg dose.¹ Bodyweight reductions with survodutide had not reached a plateau at week 46, suggesting additional weight loss could be achieved with longer treatment duration.¹

“Given the prevalence of obesity and its many disease-related complications, there is a dire need for treatments that can help treat the disease of obesity effectively,” said Carel le Roux, MD, Ph.D., Professor at University College in Dublin, Ireland, and Principal Investigator of the trial. “Current treatments for obesity mainly focus on weight loss by reducing energy intake.² By activating both the glucagon and GLP-1 receptors, survodutide may both inhibit appetite and improve energy expenditure, thereby helping to treat the disease of obesity.² These encouraging data support the further study of survodutide in larger Phase III trials.”  

After 46 weeks of treatment, up to 40% of people who reached the highest two doses of survodutide achieved a weight loss of at least 20%, versus 0% with placebo.¹ Body weight loss of 15% or more was achieved by 67% of people who reached survodutide 4.8 mg versus 4.3% of those on placebo.¹

Treatment with survodutide did not show unexpected safety or tolerability issues. Serious adverse events were reported by 4.2% of participants on survodutide versus 6.5% of those on placebo.¹ Treatment discontinuation due to adverse events occurred in 24.6% and 3.9% of participants, respectively, mainly due to gastrointestinal adverse events.¹ Most treatment discontinuations due to adverse events occurred during the rapid dose-escalation phase and may potentially be mitigated with more gradual dose escalation.¹ The adverse events reported were similar to those expected with the GLP1-R agonist class of drugs.¹

“With our long heritage in researching and developing new treatments for cardiovascular, renal, and metabolic conditions, we are extremely encouraged by these robust and compelling Phase II data,” said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. “Survodutide may become the first anti-obesity medication to reduce appetite while increasing energy expenditure through the liver. We look forward to furthering our discussions with health authorities to advance this dual receptor agonist into Phase III trials as we aim to help fill a treatment gap in this disease area.”

“Obesity is one of the most significant healthcare challenges in medicine today,” said David Kendall, M.D., Chief Medical Officer, Zealand Pharma. “At Zealand Pharma, we have both experience and success in discovering and developing peptide therapeutics that target key metabolic pathways – designed to help people living with overweight and obesity by achieving substantial weight loss while addressing the many complications of this disease.”

About the Study
The Phase II, randomized, parallel group, dose-finding study evaluated once-weekly subcutaneously administered survodutide for 46 weeks compared with placebo in people with overweight or obesity without type 2 diabetes.¹ The trial included 20 weeks of dosing escalation and 26 weeks of maintenance and evaluated doses of 0.6 mg, 2.4 mg, 3.6 mg, and 4.8 mg.¹

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.² 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.

Survodutide is also being evaluated in a Phase II study in adults with NASH and liver fibrosis (stages F1/F2/F3).³ The trial is expected to complete in Q4 2023. Survodutide has received U.S. FDA Fast Track Designation for adults with NASH.⁴

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.⁶ The World Obesity 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.⁶ Overweight and obesity are complex chronic conditions involving abnormal or excessive fat accumulation that presents a risk to a person’s overall health.⁷

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 Contacts

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

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

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References

¹ le Roux CW et al. A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study of BI 456906 in People with Overweight/Obesity. Presented at the American Diabetes Association’s 83^rd Scientific Sessions 2023; 23 June 2023. 51-OR.

² 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.

³ 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 June 2023.

⁴ 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 June 2023.

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

⁶ 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 June 2023.

⁷ 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.