Boehringer Ingelheim’s glucagon/GLP-1 dual agonist has driven 16.6% weight loss at Week 76 of a phase 3 study. While the result fell short of the bar set by existing drugs, the German drugmaker is betting that targeting glucagon will make survodutide better at cutting cardiometabolic risk than incumbent products.
Glucagon influences appetite regulation and stimulates the breakdown of fats, especially in the liver. By targeting glucagon and GLP-1, which suppresses appetite, survodutide could help people lose weight and improve liver health. Improving liver function has benefits across the body, with the organ affecting fat accumulation, inflammatory markers and other aspects of metabolic health.
The topline readout from Boehringer’s phase 3 Synchronize-1 trial offers limited insights into whether the drug candidate can deliver those benefits. At 13.4%, placebo-adjusted weight loss in 725 adults with obesity or overweight, without Type 2 diabetes, was undifferentiated.
Novo Nordisk reported (PDF) 12.4% placebo-adjusted weight loss at Week 68 of a phase 3 study of its GLP-1 drug Wegovy in a similar patient population. Eli Lilly set the standard with Zepbound, linking the dual GIP/GLP-1 receptor agonist to 17.8% placebo-adjusted weight loss at Week 72, and then raised the bar with data on its triple-G prospect retatrutide.
Survodutide may be differentiated in other ways, but that hypothesis is unconfirmed after the phase 3 readout. Boehringer reported a statistically significant drop in waist circumference, a marker of visceral fat and cardiometabolic risk, without providing data. Visceral fat contributes to metabolic dysfunction and is connected to impaired liver function. Patients on survodutide primarily lost fat, not muscle.
The results point toward areas survodutide may have an edge without providing conclusive evidence. A clearer picture may emerge as Boehringer shares data from Synchronize-1 and, in particular, posts results from other studies. The phase 3 program includes trials targeting patients with comorbidities such as liver, cardiovascular and kidney disease, plus metabolic dysfunction-associated steatohepatitis studies.
Similarly, the topline Synchronize-1 readout lacks a clear answer to questions about the tolerability of survodutide. The questions emerged after 24.6% of patients discontinued treatment in a phase 2 trial. At a Barclays event last month, the CEO of Zealand Pharma, which licensed survodutide to Boehringer, predicted more flexible titration and antiemetic drugs would help control side effects in the phase 3 trial.
It is unclear whether that prediction came true. Boehringer said that, as expected with a GLP-1 therapy, people had gastrointestinal events, with discontinuations being more frequent during dose escalation. The events were mild to moderate in severity and temporary. Boehringer has yet to share any figures on the safety and tolerability seen in the phase 3 study.
When asked by Fierce last month how survodutide could stand out from the competition, Paola Casarosa, Ph.D., the member of Boehringer’s board who oversees the company’s innovation unit, said the pharma’s “position remains clearly [that there is] a differentiation on what is the glucagon component and what is the liver health component.”
Survodutide isn’t Boehringer’s only clinical-stage bet in the obesity space. There’s also a triple agonist—although Casarosa was tight-lipped to Fierce about the exact targets of the candidate.
