Following the recommendations of an independent Data Monitoring Committee, Novo Nordisk has halted a Phase III kidney outcomes study of semaglutide ahead of schedule due to strong efficacy signals.
Pictured: Novo Nordisk building in California/iStock, hapabapa
Novo Nordisk is ending its Phase III FLOW trial ahead of schedule after an interim analysis of the kidney outcomes study of semaglutide found a very high likelihood of study success, the company announced Tuesday.
FLOW, a large randomized, double-blinded and placebo-controlled superiority trial, was assessing the effects of Novo’s GLP-1 agonist semaglutide on the progression of renal impairment and on the risk of renal and cardiovascular mortality in patients with type 2 diabetes and chronic kidney disease (CKD).
Semaglutide is the active ingredient in Novo’s diabetes drug Ozempic and weight-loss treatment Wegovy, approved in January 2020 and June 2021, respectively.
The study enrolled more than 3,500 patients worldwide and administered semaglutide as an adjunct to standard of care. FLOW’s protocol allowed for an interim analysis once a specific and pre-determined number of primary endpoint events had already occurred.
At this interim analysis, an independent Data Monitoring Committee recommended to stop FLOW early because its data “met certain pre-specified criteria for stopping the trial early for efficacy,” according to Novo’s announcement.
To preserve the integrity of the trial, Novo will stay blinded to its data while it closes out the study. The company expects to share FLOW’s readout in the first half of 2024.
Semaglutide is a therapeutic peptide that mimics the GLP-1 hormone to activate the corresponding receptor and induce the secretion of insulin from the pancreas. Through this mechanism of action, semaglutide promotes weight loss and improves blood glucose control.
The molecule has also shown promise beyond these indications. In August 2023, Novo posted data from the Phase III SELECT trial, showing that a 2.4-mg injection of semaglutide could cut the risk of major adverse cardiovascular events—comprised of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke—by 20% compared with placebo.
The company followed this up with a publication in The New England Journal of Medicine later that month. In the Phase III STEP trial, semaglutide led to significant improvements in quality of life and physical function, as measured by the cardiomyopathy questionnaire KCCQ-CSS, in patients with obesity and heart failure with preserved ejection fraction.
However, semaglutide’s strong efficacy profile also comes with substantial and emerging safety concerns. In July 2023, the U.K. launched an investigation into the potential self-harm and suicidal ideation risks that were being documented in patients taking Wegovy, Ozempic and other GLP-1 agonists. Last week, a paper published in JAMA found that this drug class might also pose a heightened risk of gastrointestinal side effects.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
