The FDA has approved a label expansion for Wegovy based on a supplemental New Drug Application (sNDA) for the indication of reducing risks of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke in adults with either overweight or obesity and established cardiovascular disease (CVD).
The approval is based on the SELECT cardiovascular outcomes trial, which demonstrated that Wegovy statistically significantly reduced the risk of MACE by 20% compared to placebo when added to standard of care. The exact mechanism of cardiovascular risk reduction has not been established.
SELECT was a randomised, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy of semaglutide 2.4mg versus placebo as an adjunct to standard of care for prevention of MACE in people with established CVD with overweight or obesity with no prior history of diabetes over a period of five years. People included in the trial were aged ≥45 years with a BMI ≥27 kg/m2.
The primary objective of the SELECT trial was to demonstrate the superiority of semaglutide 2.4mg compared to placebo with respect to reducing the incidence of three-point MACE consisting of cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke. Key secondary objectives were to compare the effects of semaglutide 2.4mg to placebo regarding mortality, heart failure, cardiovascular risk factors, including glucose metabolism, body weight and kidney function. The trial enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites. SELECT was initiated in 2018.
The findings from SELECT also showed that over a period of up to five years, risk reductions in MACE were achieved regardless of baseline age, sex, race, ethnicity, body mass index (BMI) and level of renal function impairment. In addition, 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 (Cardiovascular death superiority not confirmed (hazard ratio: 0.85 (0.71;1.01) and death by any cause not statistically significant based on the prespecified testing hierarchy (hazard ratio: 0.81 (0.71; 0.93)). Further, additional clinical data from SELECT are included in the label.
"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," said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. “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.”
Following the US label update, Wegovy is now indicated in combination with a reduced calorie diet and increased physical activity to reduce the risk of MACE in adults with established cardiovascular disease and either obesity or overweight, as well as to reduce excess body weight and maintain weight reduction long term in adults and paediatric patients aged 12 years and older with obesity and in adults with overweight in the presence of at least one weight-related comorbid condition.
Novo Nordisk has also filed for a label expansion in the EU, and a decision is expected in 2024.