Novo Nordisk is running into a speed bump with Wegovy’s label expansion efforts in heart disease as it has pulled its FDA submission in heart failure with obesity and will refile at the start of 2025.
In addition, due to “portfolio prioritizations,” it cut a Phase 1 trial studying a once-monthly GLP-1/GIP agonist, the company disclosed as part of its earnings report. It will also no longer move forward with a VAP-1 inhibitor in metabolic dysfunction-associated steatohepatitis, or MASH, from which it grabbed an exclusive license from the Japanese company UBE Industries back in 2019.
As it continues to report megablockbuster revenue from its GLP-1 franchise, Novo has been looking to build on its lead with a pipeline of follow-on candidates with improved dosing timelines and alternative mechanisms of action. It has also been running studies that look to validate its GLP-1 drugs’ broader cardiometabolic impact beyond diabetes and weight loss, as well as testing out new modalities in those areas.
The Danish pharma giant filed data from the STEP-HFpEF trials for Wegovy in January both in the US and EU. But after talks with the FDA, the company has withdrawn its application and will reapply in 2025 with more data, such as those from the FLOW trial that investigated semaglutide in chronic kidney disease in patients with type 2 diabetes.
Novo decided to withdraw the result from the STEP-HFpEF trials for regulatory review in the US “to further substantiate the likelihood of getting hard endpoints into the label update,” said Martin Holst Lange, EVP and head of development, during its earnings call.
The company revealed Phase 3 STEP-HFpEF data last August, which showed that semaglutide can offer weight loss and spur heart improvements. In the heart failure-specific primary endpoint of change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) — which measures issues relevant to heart failure patients, from symptoms to quality of life — semaglutide offered a 16.6 point change versus 8.7 points with placebo (p<0.001) at 52 weeks.
As for the Phase 3 FLOW trial, Novo detailed cardiovascular data from the study in May. In a secondary endpoint, semaglutide patients had an 18% lower risk of a major cardiovascular event compared with placebo (p=0.029).
In March, Wegovy’s US label was expanded to add reduced risk of a major adverse event in people who are with cardiovascular risk and are also overweight or obese, based on data from the Phase 3 SELECT trial.
Elsewhere, with Novo ditching its monthly subcutaneous GLP-1/GIP receptor agonist, it will be left with a once-weekly version that’s in a Phase 2 trial. Eli Lilly’s tirzepatide is also a GLP-1/GIP agonist.
In MASH, Novo has more options, with semaglutide in a Phase 3 trial and an FGF21 analog in a mid-stage test. It also has an NLRP3 inhibitor, a siRNA that targets LXR-alpha and a MARC1 asset in Phase 1.
The abandoned MASH candidate, named UD-014, was designed to inhibit vascular adhesion protein-1, with preclinical studies showing it may address the inflammatory aspect of the liver disease. There are data suggesting that VAP-1 is at higher levels in patients with nonalcoholic fatty liver disease compared with those who don’t.
The Phase 1 study was stopped “after the first part of the study which evaluated safety, tolerability, pharmacokinetics and pharmacodynamics of VAP-1i,” Novo wrote.
Additional reporting by Kyle LaHucik
Editor’s note: This article was updated to clarify a quote from the company’s earnings call.