Lilly and Boehringer attract local trials to tackle obesity and its cardiovascular risks

Obesity remains a pressing public health issue, serving as a key driver of numerous complications, including atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). Australia is home to two phase 3 clinical trials led by Eli Lilly and Boehringer Ingelheim which are exploring innovative therapies aimed at addressing obesity and associated cardiovascular risks.

Two in three Australians living with obesity and overweight, costing the nation $12 billion annually.

The recent success of obesity treatments such as Novo Nordisk’s Wegovy (semaglutide) and Lilly’s Mounjaro (tirzepatide) has accelerated the pursuit of new therapies. Experts suggest that novel medicines targeting multiple pharmacologic pathways could offer greater efficacy than those focused solely on the GLP-1 receptor.

Previous cardiovascular trials have shown that GLP-1 receptor agonists (GLP-1 RAs) can lower ASCVD risk in patients with type 2 diabetes. More recently, research has demonstrated that these therapies may also reduce cardiovascular risk in patients with obesity who do not have diabetes.

Lilly’s TRIUMPH-3 phase 3 trial is evaluating retatrutide, a once-weekly GLP-1 receptor agonist, in patients with obesity and established cardiovascular disease (CVD). What sets retatrutide apart from existing treatments such as Wegovy and Saxenda (liraglutide) is its triple-agonist (triple-G) mechanism of action. In addition to targeting the GLP-1 receptor, the drug also activates the gastric inhibitory polypeptide receptor (GIPR) and the glucagon receptor (GCGR).

Phase 2 trial results for retatrutide are promising, showing a weight reduction of up to 17.5% with the 12mg dose, compared to a mere 1.6% reduction in the placebo group over 24 weeks. If the ongoing phase 3 trial demonstrates similar success, retatrutide could emerge as a strong competitor in the obesity market.

Meanwhile, Boehringer Ingelheim’s SYNCHRONIZE-CVOT phase 3 trial is investigating survodutide, a subcutaneous GLP-1 receptor dual agonist, in patients with obesity or overweight and coexisting cardiovascular disease, chronic kidney disease, or cardiovascular risk factors.

In a phase 2 study, survodutide – co-invented by Boehringer Ingelheim and Zealand Pharma – led to a 19% reduction in weight after 46 weeks of treatment. The phase 3 trial’s primary endpoint is the time to the 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, or heart failure events.

Should SYNCHRONIZE-CVOT confirm survodutide’s noninferiority for 5P-MACE and highlight additional benefits for heart failure symptoms, the therapy may become another new option for obesity management and the associated cardiovascular risks.

A key question remains: Should the government fund obesity and overweight treatments, currently absent from the PBS?

Associate Professor Priya Sumithran, an endocrinologist and clinician researcher at Monash University, said “Obesity is a complex, chronic disease that can seriously impair health and wellbeing. Several effective, evidence-based medications are approved, and recommended in Australian (and international) guidelines, for obesity management. But, since none are listed on the PBS, only people who can afford to pay hundreds of dollars per month can use them.”

Professor John Dixon, Vice President of the National Association of Clinical Obesity Services, stated “Australia has one of the highest rates of obesity in the world. Not only is obesity a complex topic which is greatly misunderstood, it requires early and long-term evidence-based care as any other chronic medical condition.

“There is a substantial unmet need to address this chronic and complex disease, and early intervention may help reduce the risk of many other serious conditions.”

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