Novo rekindles heart failure hopes for semaglutide with new pooled analysis

After a regulatory hiccup earlier this month, Novo Nordisk’s heart failure ambitions for its obesity star Wegovy (semaglutide) are starting to get back on track.

Novo’s semaglutide cut the risk of combined cardiovascular (CV) death or worsening heart failure (HF) events by 31%, based on an incident rate of 5.4% in semaglutide patients versus 7.5% in those on placebo, the company said Friday.

Semaglutide also led to a 41% lower risk of worsening HF, according to a pooled analysis of four Novo Nordisk trials.

That said, the GLP-1 medicine had “no significant effect” on the incidence of CV death, per Novo.

Novo’s post-hoc data drop, which was published in the Lancet Friday, looked at heart failure outcomes in a total of 3,743 patients with a history of HFpEF across two semaglutide doses—2.4 mg in the SELECT, STEP-HFpEF and STEP-HFpEF DM trials and 1 mg in the FLOW study.

For patients with heart failure with preserved ejection fraction, or HFpEF, the heart muscle contracts properly but the ventricles don’t relax, causing diminished blood flow. Obesity could be a key driver of HFpEF, with Novo estimating in a press release that roughly 80% of patients suffering from the heart failure condition are also overweight or obese. Type 2 diabetes is also associated with the condition and can lead to greater symptom burden, worse functioning for patients and a “more severely impaired quality of life,” Novo said.

The data drop follows the company’s decision to pull its Wegovy filing in heart failure patients. Earlier this month, Novo reported in its quarterly earnings presentation that it was pulling the filing following discussions with the FDA. Wegovy for obesity and Ozempic for type 2 diabetes both utilize the molecule semaglutide at different doses.

Despite “very strong data” for semaglutide in reducing the risk of CV death or hospitalization for heart failure, the “reasonably small” size of Novo’s studies prompted the company to pump the brakes on its filing, Novo’s development chief, Martin Holst Lange, said on a conference call in early August. 

At the time, Novo said it aimed to resubmit its application in early 2025, leveraging data from trials including FLOW, which is evaluating kidney outcomes with a once-weekly, 1-mg injection of semaglutide.

The filing pause came after Novo in the summer of 2023 posted results from the phase 3 STEP-HFpEF trial showing that a weekly 2.4-mg dose of semaglutide bested placebo at reducing symptoms and physical limitations in patients with obesity and HFpEF.

Elsewhere, in the FLOW trial for chronic kidney disease patients, those who received a 1-mg dose of semaglutide saw a reduction in risk of major cardiovascular events by 18% and all-cause mortality by 20%.

Meanwhile, Wegovy snared a new cardiovascular nod back in March, making it the first weight-loss drug to score FDA approval for risk reduction of cardiovascular death, heart and stroke in adult patients with CV disease who have obesity or are overweight.

Still, the pressure is on for Novo after its chief rival, Eli Lilly, recently showed in a late-stage trial that its GLP-1/GIP treatment tirzepatide cut the risk of adverse HF outcomes by 38% versus placebo. Earlier this summer, Lilly said it planned to submit the results to the FDA and other regulators “starting later this year.”