Novo Nordisk withdraws its FDA heart failure application for Wegovy

Novo Nordisk has pulled its request asking the FDA to approve Wegovy (semaglutide) for treating heart failure, the company said in its quarterly earnings presentation on August 7, 2024 ^[1]. After talks with the agency, Novo said it plans to resubmit the application in early 2025, this time including new data from a separate kidney trial ^[1].

The withdrawal follows FDA feedback that the studies backing the application were "reasonably small" and did not include enough total cardiovascular events to substantiate that semaglutide actually treats heart failure, according to Martin Holst Lange, Novo's development chief, who spoke on a conference call ^[1]. Novo had based its filing on two trials: one in patients with heart failure and type 2 diabetes, and another in non-diabetic patients with heart failure who were obese or overweight ^[1]. A combined analysis of the two trials showed a 69% decrease in the risk of cardiovascular death or hospitalization for heart failure, which Holst Lange called "absolutely very strong data" ^[1]. Even so, the FDA wanted more evidence that the effect would hold up in a larger, event-driven analysis ^[1].

One of the underlying studies, the phase 3 STEP HFpEF trial reported in August 2023, found that a weekly 2.4-mg dose of semaglutide—the same dose used in Wegovy—reduced symptoms and physical limitations better than placebo in patients with obesity and heart failure with preserved ejection fraction (HFpEF) ^[1]. Patients on semaglutide in that trial lost an average of 13.3% of body weight over a year, compared with 2.6% in the placebo group ^[1]. HFpEF makes up roughly half of all heart failure cases, and about 80% of those patients are obese or overweight ^[1].

Novo said the resubmission will draw on additional data from its FLOW trial, which tested a 1-mg weekly dose of semaglutide in patients with chronic kidney disease ^[1]. In that trial, semaglutide cut the risk of major cardiovascular events by 18% and all-cause mortality by 20%, and it slowed the decline in kidney function as measured by estimated glomerular filtration rate ^[1].

Why it matters for patients

This withdrawal means Wegovy does not currently carry an FDA-approved indication for treating heart failure, so patients cannot expect that specific label change soon ^[1]. The delay does not affect Wegovy's existing approval, granted in March 2024, to reduce cardiovascular risk in adults with established heart disease who are obese or overweight ^[1]. For people with heart failure and obesity who are already prescribed Wegovy off-label or under that broader cardiovascular indication, the underlying trial data reported so far—including the symptom and weight-loss results from STEP HFpEF—remain part of the public record, even though the FDA has not yet accepted them as sufficient to prove a heart failure treatment effect ^[1].

Insurance coverage is one area where this matters. The article notes that payers have been reluctant to cover GLP-1 drugs for weight loss, and that coverage is expected to expand if these drugs are shown to help with heart and kidney problems ^[1]. A delayed heart failure approval could slow that shift for Wegovy specifically, even as competing evidence emerges for other drugs in the class.

Novo is not alone in this race. Eli Lilly reported in late July 2024 that tirzepatide (sold as Mounjaro and Zepbound) reduced the risk of adverse heart failure outcomes by 38% compared with placebo in a separate phase 3 trial, and the company said it planned to submit those results to the FDA and other regulators later that year ^[1].

What happens next

Novo said it expects to resubmit its heart failure application for Wegovy in early 2025, incorporating additional data from the FLOW kidney trial ^[1]. The sources do not specify an exact submission date or say how the FDA will respond, so the timeline and outcome of any renewed review are not yet known.