Boehringer Ingelheim and Zealand Pharma have launched three pivotal phase 3 trials for their obesity drug candidate survodutide, marking a significant step toward entering the rapidly expanding obesity therapeutics market. The glucagon/GLP-1 receptor dual agonist, also designated as BI 456906, demonstrated up to 19% weight loss in phase 2 trials presented at the American Diabetes Association congress in June.
SYNCHRONIZE Trial Program Targets Diverse Patient Populations
The comprehensive phase 3 program encompasses three distinct studies designed to evaluate survodutide's efficacy across different patient populations. SYNCHRONIZE-1 will recruit patients who are overweight or obese without diabetes, while SYNCHRONIZE-2 focuses on those with concurrent type 2 diabetes. The third study, SYNCHRONIZE-CVOT, represents a long-term cardiovascular outcomes trial examining the drug's effects in patients with or at risk of cardiovascular disease and chronic kidney disease.
According to clinicaltrials.gov, SYNCHRONIZE-1 and SYNCHRONIZE-2 are scheduled for completion in 2025, while the cardiovascular outcomes study is expected to require several additional years to generate definitive results.
Competitive Positioning in Emerging Obesity Market
The advancement positions Boehringer and Zealand to compete directly with market leaders Novo Nordisk and Eli Lilly, who currently dominate the new generation of obesity therapies. Novo Nordisk's Wegovy (semaglutide), a GLP-1 agonist already approved for obesity, faces significant supply constraints due to overwhelming demand. Meanwhile, Eli Lilly's Mounjaro (tirzepatide), a dual GIP/GLP-1 agonist approved for diabetes, awaits FDA approval for obesity treatment.
"As the prevalence of the disease of obesity continues to increase, it is imperative that we develop additional innovative approaches to address this serious, chronic disease," said Carel le Roux, consultant in metabolic medicine at University College Dublin and principal investigator of the phase 2 trial.
Novel Mechanism Offers Potential Differentiation
Survodutide's dual mechanism targeting both glucagon and GLP-1 receptors may provide distinct advantages over existing therapies. The companies suggest it could become the first obesity treatment capable of both reducing weight and curbing appetite while increasing liver energy expenditure. Like competing therapies, survodutide is administered as a once-weekly subcutaneous injection.
Phase 2 data revealed additional benefits beyond weight reduction, including decreases in waist circumference and blood pressure, supporting the drug's potential for comprehensive metabolic improvement.
Tolerability Challenges Require Strategic Dosing Modifications
The phase 2 results highlighted a significant tolerability concern, with approximately 25% of patients receiving the highest dose discontinuing treatment, primarily due to gastrointestinal side effects, compared to 4% in the placebo group. These discontinuations predominantly occurred during the dose-escalation phase, suggesting that modified dosing strategies could improve patient retention.
Boehringer has indicated plans to extend the dose escalation period from two to four weeks in phase 3 trials to enhance tolerability while maintaining efficacy. This approach reflects lessons learned from the phase 2 experience and could prove crucial for the drug's commercial viability.
Market Opportunity Drives Industry Investment
The World Obesity Federation projects that 2.7 billion adults could be living with overweight or obesity by 2025, creating substantial healthcare and economic burdens. Market analysts predict the obesity therapeutics sector could generate tens of billions of dollars annually within the next decade, providing ample opportunity for multiple successful products.
The competitive landscape continues to evolve rapidly, with Novo Nordisk advancing CagriSema, a combination of semaglutide and amylin analogue cagrilintide, through phase 3 trials. Eli Lilly is simultaneously developing retatrutide, a triple agonist targeting GLP-1, GIP, and glucagon receptors. Additionally, multiple companies are pursuing oral GLP-1 agonists to address patient preferences for non-injectable treatments.
Despite entering the race behind established competitors, Boehringer and Zealand's differentiated approach with survodutide could capture significant market share in this expanding therapeutic area, particularly if the modified dosing strategy successfully addresses tolerability concerns while maintaining the impressive weight loss efficacy demonstrated in phase 2 trials.
