Novo Nordisk withdraws Wegovy heart failure application and plans 2025 resubmission
Wegovy still is not approved to treat heart failure, and payers often look for heart and kidney benefits when deciding whether to cover these drugs.
Novo Nordisk has withdrawn its application asking the FDA to approve Wegovy for a common form of heart failure, after the agency said the company's trials were too small to confirm that the drug changes heart-related outcomes. Novo said on Aug. 7, 2024, that it expects to resubmit the filing in early 2025 [1].
The decision was disclosed in the company's quarterly earnings presentation. Martin Holst Lange, Novo's development chief, told analysts on a conference call that a combined analysis of two trials showed a 69% decrease in the risk of cardiovascular death or hospitalization for heart failure. "When we did the meta analysis of the two trials, we see a 69% decrease in risk of CV death or hospitalization for heart failure, so absolutely very strong data," he said [1]. But the trials were "reasonably small," he added, and the FDA wanted a larger number of total cardiovascular events before accepting the treatment's effect [1].
The two studies covered different groups: one enrolled patients with heart failure and type 2 diabetes, and the other enrolled non-diabetic patients with heart failure who were obese or overweight [1]. The target condition, heart failure with preserved ejection fraction (HFpEF), accounts for roughly half of all heart failure cases, and about 80% of those patients are obese or overweight, according to the company [1]. The number of patients enrolled in the two trials has not been reported.
In August 2023, Novo reported results from the phase 3 STEP HFpEF trial, which found that a weekly 2.4-milligram dose of semaglutide, the same dose used in Wegovy, did better than placebo at reducing symptoms and physical limitations in patients with obesity and HFpEF. Patients taking semaglutide lost an average of 13.3% of their body weight over a year, compared with 2.6% for those on placebo [1].
The resubmission will include data from the FLOW trial, which tested a once-weekly 1-milligram injection of semaglutide, a different dose from Wegovy's, in people with chronic kidney disease. In FLOW, the risk of major cardiovascular events fell 18% and the risk of death from any cause fell 20% with semaglutide compared with placebo. Kidney function also declined "significantly slower" on semaglutide, as measured by estimated glomerular filtration rate [1].
Wegovy was approved in March 2024 to reduce the risk of cardiovascular events in adults with established heart disease who are obese or overweight, and a heart failure approval had been expected to follow the two trials [1]. Novo is competing with Eli Lilly, which reported in late July 2024 that in a phase 3 trial, its drug tirzepatide (sold as Mounjaro for type 2 diabetes and Zepbound for obesity) reduced the risk of adverse heart failure outcomes by 38% compared with placebo. Lilly said it plans to submit those results to the FDA and other regulators "starting later this year" [1].
Why it matters for patients
This withdrawal does not change what Wegovy is currently approved for. The drug is not approved to treat heart failure, and the FDA's request for more data means that remains the case.
The kind of evidence gathered in the STEP HFpEF and FLOW trials can influence insurance coverage. Payers have been reluctant to cover drugs prescribed for weight loss, and coverage is expected to become more widely available if the treatments are shown to help people with heart and kidney problems [1]. Whether a future heart failure approval would change coverage for semaglutide has not been reported.
The FDA's concern was about the number of cardiovascular events recorded in the trials, not a finding that the drug did not work. Novo's own analysis of the two trials pointed to a large reduction, while the agency wanted more events to confirm it [1]. How many additional events the FDA is seeking, and from which studies, has not been disclosed.
What happens next
Novo expects to resubmit the application in early 2025, adding data from FLOW [1]. Lilly has said it plans to begin submitting tirzepatide's heart failure results to the FDA and other regulators later in 2024 [1]. When the FDA might act on either filing has not been reported.
Sources
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