Boehringer Ingelheim is gearing up to take survodutide to regulators next year after the obesity drug proved its cardiovascular (CV) credentials in its latest phase 3 study.
The German drugmaker arrived at the American Heart Association Scientific Sessions in Chicago on Monday armed with the results from a late-stage trial designed to prove that survodutide—a glucagon/GLP-1 receptor dual agonist—doesn’t increase the risk of major adverse CV events.
The Synchronize-CVOT study enrolled 5,530 adults with obesity or overweight with established CV disease or chronic kidney disease, and/or at least two weight-related complications or risk factors for CV disease. Participants received a weekly injection of survodutide at either a 3.6 mg or 6 mg dose, or placebo, over 72 weeks.
The study demonstrated a hazard ratio of 0.89 when comparing the time to first occurrence of CV death, non-fatal stroke, non-fatal heart attack or ischemia-related coronary revascularization, meeting the primary endpoint. The study also hit all secondary endpoints, including those looking at a range of cardiometabolic health markers such as inflammatory marker high-sensitivity C-reactive protein and triglycerides.
Neerja Balachander, M.D., Ph.D., who oversees clinical development medical affairs for cardio-renal-metabolism at Boehringer, told Fierce in an interview ahead of the readout that she was “super thrilled by the result,” noting that this was the first-ever global CV safety trial of a glucagon/GLP-1 dual agonist.
The company had launched the study as part of its “commitment to healthcare authorities” to provide a well-rounded package of data for the drug, and before it became clear from Boehringer’s other studies that glucagon agonists can reduce blood glucose levels, Balachander said.
“We proactively agreed to a study where we would show … a panel of all these metabolic markers,” she added. “As the data have unfolded, we have, much to our relief and satisfaction, a more compelling story than we had at the outset.”
“This completes our exciting package for survodutide and, fingers crossed, we will be looking to talk to the authorities,” Balachander said.
While the rest of the study’s results were broadly in line with previous late-stage trials for the obesity drug, they will be unlikely to allay lingering concerns about how the therapy will compete in such a competitive weight loss landscape.
Boehringer said Monday that the Synchronize-CVOT study demonstrated “meaningful” weight loss of up to 13.7% at Week 72, compared to 2% for the placebo cohort. This falls slightly below the 15% touted by Eli Lilly’s blockbuster Zepbound over the same time period, with the caveats that cross-trial comparisons bring. But Balachander is unfazed by the match-up.
“Our frame here is that every patient’s weight loss journey is going to be unique,” she told Fierce. “For instance, if you are a patient that needs [a] sort of that bariatric surgery effect, then survodutide might not be your answer.”
“We have another answer in our portfolio for you for that,” continued Balachander, alluding to a triple agonist of GLP-1, GIP and NPY2 receptor, dubbed BI 3034701, which entered a phase 2 study in July.
“What we are here for [with survodutide] is those people that want to lose the metabolically bad fat and want to conserve muscle,” she said. This ability to spare muscle—a holy grail of next-gen obesity drugs—was hinted at in a previous readout back in June.
But the Synchronize-CVOT results will also do little to resolve concerns about the tolerability profile of survodutide, with 19.3% and 20.8% of patients in the 3.6 mg and 6 mg cohorts, respectively, discontinuing treatment over gastrointestinal (GI) adverse events, compared to 1.9% of the placebo arm.
This doesn’t match up well with either Zepbound or Novo’s Wegovy, which saw discontinuations due to AEs range from 2.6% to 7.1% depending on the dose.
But Balachander is “very confident” that this tolerability profile will improve in upcoming trials where healthcare professionals can amend dosing levels when patients experience any GI effects before they reach the point of discontinuation.
Survodutide continues to be evaluated in a clutch of other phase 3 studies, ranging from liver disease to diabetes and women’s health.
A key part of this strategy is exploring the therapy’s potential to treat the fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH). Boehringer isn’t the only company to have had this idea, with Wegovy already approved for the condition, while Lilly is exploring the potential of both Zepbound and its triple-G agonist retatrutide in this space.
Balachander explained to Fierce that Boehringer is taking a two-pronged approach of trying to get survodutide approved by the FDA for both weight loss and MASH. The aim is to submit an approval application to treat weight loss “at some time in the next year.”
“If we could, we would do it as soon as possible,” she explained. “But as you know, it’s a conversation with the regulators, and we are responsible for a complete package with them.”
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