Katherine Lewin | News Reporter
Novo Nordisk’s GLP-1 Wegovy has shown cardiovascular benefit again, this time in the Phase III STEP HFpEF trial, on top of the expected weight loss, the company announced at the European Society of Cardiology (ESC) Congress today.
Against placebo, 2.4 mg of Wegovy (semaglutide) showed “large” reductions in heart failure-related symptoms and physical limitations, as well as improvements in exercise function and weight loss in adults with heart failure with preserved ejection fraction (HFpEF) and obesity.
The data from the STEP trial come just a few weeks after Novo reported positive data from a different cardiovascular outcomes trial with the same dose of semaglutide, paving the way to extend the reach of the drug — already a megablockbuster — to cardiovascular diseases. Florian Baeres, VP of global medical affairs, diabetes, cardiovascular and Alzheimer’s disease at Novo Nordisk, told Endpoints News the company is also testing in a different patient population.
“We have the STEP HFpEF trial right now which is focused on a population with obesity and heart failure with preserved ejection fraction but we also have another trial that is ongoing that looks at a similar population, also with heart failure with preserved ejection fraction and obesity, but who also have type 2 diabetes,” Baeres said. “The data sets from both of these trials will be used to pursue a regulatory interaction to ultimately allow us to bring this forward to patients.”
Heart failure study
The STEP trial included patients with HFpEF and a BMI of 30 or higher. Patients were randomized to receive either semaglutide or placebo for 52 weeks.
Novo used the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) as a co-primary endpoint to measure symptoms and physical limitations of HFpEF. In the 529-patient trial, patients on semaglutide saw a 16.6-point increase at 52 weeks on the questionnaire, compared to an 8.7-point increase in the placebo arm, earning a p<0.001.
Investigators also looked for changes in patients’ six-minute walking distance test, a secondary endpoint. For the patients on semaglutide, there was a mean increase in the distance walked of 21.5 meters versus 1.2 meters with placebo.
Patients saw a mean reduction in body weight of 13.3% with semaglutide versus a 2.6% reduction with the placebo, as well as a reduction in C-reactive protein levels, indicating lower inflammation.
Novo said the safety profile was similar to other semaglutide studies. Serious adverse events were reported in 35 participants, 13.3%, in the semaglutide group and 71, 26.7%, in the placebo group.
Florian Baeres
“I think when we talk about the observed effect, it’s also important that we acknowledge that semaglutide-derived weight loss, but there’s also other attributes to semaglutide that are likely to have contributed to the effect that we have seen,” Baeres said.
Label expansion
New data on semaglutide have been shedding light on the GLP-1 receptor agonist’s potential in improving cardio health. In the vast SELECT trial, semaglutide reduced major adverse cardiovascular events by 20% in obese or overweight patients without diabetes.
The SELECT trial easily hit its primary endpoint, reduction in major adverse cardiovascular events (MACE), which includes cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, compared with placebo. It enrolled 17,604 adults who were 45 years or older, overweight or obese, and had a diagnosis of cardiovascular disease.
Novo said it plans to file for a label expansion in the US and EU this year with data from the SELECT trial. The full study is likely to be presented at the American Heart Association conference in November, and that readout should include secondary endpoints, like mortality, cardiovascular risk factors, glucose metabolism, body weight and renal function.
Data from the STEP HFpEF trial will also be sent to regulators, Baeres added.
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