Semaglutide 2.4 mg (Wegovy) Wins Expanded Indication to Include Reduced Risk of MACE

Semaglutide 2.4 mg (Wegovy; Novo Nordisk) today was granted an expanded indication from the US Food and Drug Administration (FDA) to include reducing the risk of major cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke in adults with cardiovascular disease and obesity or overweight.¹

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The label extension marks a first for the FDA—approval of a treatment to reduce CV risk specifically in the high-risk population of individuals with overweight or obesity. Data for the decision comes from the phase 3 SELECT cardiovascular outcomes trial with once weekly subcutaneous semaglutide, which demonstrated statistically significantly reduced the risk of MACE by 20% compared to placebo when added to standard of care, according to an announcement from Novo Nordisk.²

Further, SELECT investigators found that over 5 years of study the reductions in risk of MACE were reached regardless of participants’ baseline age, sex, race, ethnicity, body mass index (BMI) and level of renal function. SELECT participants did not have diabetes.²

"We are very pleased that Wegovy is now approved in the US as the first therapy to help people manage their weight and reduce cardiovascular risks," Martin Holst Lange, executive vice president and head of Development at Novo Nordisk said in the release.²

“This approval is an important milestone for people living with obesity and cardiovascular disease, as the SELECT data demonstrated that Wegovy has the potential to prolong lives by addressing some of the leading causes of preventable deaths by reducing the risks of cardiovascular events.”²

The label is updated to include data from SELECT showing a risk reduction in cardiovascular death by 15% and a risk reduction of death from any cause by 19%, both compared to placebo.

Semaglutide, a glucose-like peptide-1 (GLP-1) receptor agonist was approved in 2021 as an adjunct to diet change and increased exercise for weight management in adults with obesity or with overweight with at least one weight-related comorbidity. It marked the first such FDA approval since 2014. The landmark approval was based on results of the STEP clinical trial program and was followed at the end of 2022 by approval of the agent for obesity treatment in youth aged 12 years and older.3

SELECT⁴

The SELECT trial included 17 604 participants aged 45 years or older with preexisting CV disease and a BMI of 27 or more but with no history of type 2 diabetes. The cohort was randomly assigned in a 1:1 ratio to receive either subcutaneous semaglutide 2.4 mg or placebo. Mean follow up was approximately 40 months and the primary endpoint was a composite of CV events.⁴

Semaglutide was associated with a 20% relative reduction in risk of a primary endpoint event, with events occurring among 6.5% of the semaglutide group and 8.0% of the placebo group (HR, 0.80; 95% CI, 0.72 to 0.90; P <. 001).3 Results also included nonsignificant trends toward benefit for CV death, heart failure hospitalization or ED visit, all-cause mortality.⁴

“Wegovy is now the first weight loss medication to also be approved to help prevent life-threatening cardiovascular events in adults with cardiovascular disease and either obesity or overweight,” said John Sharretts, MD, director of the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.

“This patient population has a higher risk of cardiovascular death, heart attack and stroke. Providing a treatment option that is proven to lower this cardiovascular risk is a major advance for public health.”

Novo Nordisk has also filed for a label expansion in the European Union and expects a decision on its application later in the year.

References

1. FDA approves first treatment to reduce risk of serious heart problems specifically in adults with obesity or overweight. News release. U.S. Food and Drug Administration. March 8, 2024. Accessed March 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or

2. Wegovy approved in the US for cardiovascular risk reduction in people with overweight or obesity and established cardiovascular disease. News release. Novo Nordisk. March 8, 2024. Accessed March 8, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html

3. Halsey G. Semaglutide cuts cardiovascular risk by 20% in adults with obesity, CVD, and without diabetes. Patient Care. November 13, 2023. Accessed March 8, 2024. https://www.patientcareonline.com/view/semaglutide-cuts-cardiovascular-risk-by-20-in-adults-with-obesity-cvd-and-without-diabetes

4. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. NEJM. Published online November 11, 2023. doi:10.1056/NEJMoa2307563