Novo Nordisk announced this week that its phase 3 trial of ocedurenone for treatment of high blood pressure in chronic kidney disease has failed.
The trial failure is a significant loss for the company, which stated that the loss would amount to approximately US $819 million.
The double blind, placebo-controlled trial, CLARION-CKD, included 652 adults with stage 3b/4 chronic kidney disease and uncontrolled hypertension and was originally supposed to run for 24 weeks.
The trial investigators had planned an interim analysis of results at week 12 and after this point an independent data monitoring committee decided that the trial should be stopped as there was not sufficient improvement in blood pressure in the treatment arm of the study.
Expanding metabolic and cardiovascular pipeline
Novo Nordisk is well known for its successful diabetes and weight loss drugs, most recently the huge success of glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, approved previously in 2017 for treatment of type 2 diabetes (Ozempic) and more recently in 2021 as an anti-obesity drug (Wegovy). Already very profitable, the company’s profits increased by 45% compared to the previous year in the first half of 2023 and earlier this month the firm announced a $4.1BN investment in a new manufacturing facility in the US.
Since then, Novo Nordisk has acquired a number of smaller companies, for example, Inversago Pharma, Embark Biotech, Catalent and Cardior Pharmaceuticals, with a view to expanding its metabolic and cardiovascular therapeutic pipeline. It has also purchased therapeutic assets such as ocedurenone, which it acquired from Singapore-based KBP Biosciences in October last year in a deal worth up to US $1.3 billion.
Development of ocedurenone
Hypertension in people with CKD can lead to additional health risks in this vulnerable population group, for example hyperkalemia (higher than normal potassium in the blood), which can cause a number of health issues including muscle problems, paralysis, cardiac arrhythmias, and sudden cardiac death.
Many renin-angiotensin-aldosterone system inhibitors, used to treat hypertension and other related cardiovascular disorders, raise the risk of hyperkalemia in people with CKD.
Ocedurenone, a non-steroidal, mineralocorticoid receptor antagonist, with a long half-life and high mineralocorticoid receptor affinity, was developed to treat hypertension and other cardiovascular disorders. There were hopes it would be particularly suitable for treating hypertension in patients with CKD, because previous trials suggested it reduced systolic blood pressure, but did not significantly increase risk of hyperkalemia.
The late-stage CLARION-CKD trial failure is a big disappointment for those involved, particularly as it has been tested in nine trials prior to CLARION-CKD and met its primary endpoint in the phase 2b BLOCK-CKD trial of a statistically significant improvement in systolic blood pressure in adults with stage 3b/4 chronic kidney disease and uncontrolled hypertension.
Novo Nordisk will now consider how and whether to develop ocedurenone for other indications.
