Finerenone

Dive Brief:Novo Nordisk will end a Phase 3 clinical trial of a hypertension drug it bought for up to $1.3 billion last year because treatment didnt appear to be working, the company said Wednesday.The decision was based on an interim data analysis by study monitors, which revealed the drug, called ocedurenone, met the trials futility criteria, indicating treated participants didnt experience a greater drop in blood pressure than those given placebo.The company will take an accounting charge of 5.7 billion Danish kroner, or about $817 million, on its second quarter earnings to offset the loss of valuation represented by ocedurenone. The charge will lower Novos operating profit guidance by 6 percentage points from the 22% to 30% it forecast in May.Dive Insight:Novo bought ocedurenone from Singapore-based KBP Biosciences, one of a string of acquisitions made as it seeks to put profits from its diabetes and obesity drugs Ozempic and Wegovy to work.When Novo announced the deal, KBP had already begun a Phase 3 trial of ocedurenone in people with chronic kidney disease and hypertension that couldnt be controlled with at least two medications. Results from a Phase 2 study of 162 people had shown ocedurenone lowered blood pressure in that population by 10 points more than a placebo.The larger Phase 3 study, intended to confirm the earlier findings, enrolled 652. The decision to terminate the trial was based on an interim analysis investigators set up before it began, which involved measuring blood pressure after 12 weeks of treatment for a difference between study volunteers taking ocedurenone and those on placebo.Had the drug shown signs of benefit at 12 weeks, the study would have evaluated blood pressure again between 48 and 52 weeks to determine how well it worked.Novo said it is still evaluating next steps for ocedurenone in other indications. When the two companies agreed on the deal, Novo executives had said they intended to initiate Phase 3 trials in cardiovascular disease and other kidney disease settings.People with chronic kidney disease and hypertension often take multiple drugs to lower blood pressure, including medicines called angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, calcium channel blockers or beta blockers. Ocedurenone is a type of diuretic called a mineralocorticoid receptor antagonist a similar mechanism of action to Bayers recently approved Kerendia. '

While semaglutide has already enjoyed ample popularity, “I do believe that these results really move the needle,” Novo Nordisk's executive medical director Michael Radin, M.D., said. While it’s hard to overstate the success Novo Nordisk’s GLP-1 franchise has already achieved, the company’s latest deep dive into semaglutide data in chronic kidney disease (CKD) could help set a new standard for “holistic” care for many diabetes patients, the company’s executive medical director, Michael Radin, M.D., told Fierce Pharma. Early Friday, Novo shared full results from the FLOW trial assessing the ability of once-weekly semaglutide 1.0 mg to help combat major kidney outcomes such as kidney failure, loss of kidney function and death from kidney or cardiovascular causes in people with Type 2 diabetes and CKD. Of note in the latest data drop, semaglutide helped slash the risk of major cardiovascular events by 18% and reduced the risk of all-cause mortality by 20%. Further, the rate of kidney function decline over time was “significantly slower” with semaglutide versus placebo, as tracked by estimated glomerular filtration rate—a common measure of kidney function—Radin said. Novo presented its detailed look at the FLOW results at the 61st meeting of the European Renal Association. The data were also published Friday in The New England Journal of Medicine. The full results come after Novo shared headline data in March that found semaglutide reduced the risk of kidney disease progression and kidney and cardiovascular death by 24%. Back in October, the company halted its FLOW trial early thanks to a positive efficacy signal. While semaglutide has already enjoyed ample popularity and uptake, “I do believe that these results really move the needle,” Radin said. “In other words, Type 2 diabetes doesn’t exist in a vacuum: These patients often have concomitant cardiovascular disease, they have chronic kidney disease, and there’s a move in the medical community to be able to treat these patients holistically,” he explained. CKD affects more than 800 million people worldwide, according to Novo Nordisk. Some 40% of patients with Type 2 diabetes also have CKD, many of whom will eventually require dialysis, Radin noted. Those patients are also more likely to die of cardiovascular death. In Radin’s eyes, the FLOW data make "semaglutide stand out uniquely amongst the options that are available for patients with type 2 diabetes and chronic kidney disease.” The medical director pointed to other pillars of care for CKD, including Bayer’s Kerendia (finerenone), RAS inhibitors and SGLT2 inhibitors, which each come with shortcomings. Kerendia and RAS drugs can't help with glycemic control, Radin said, whereas SGLT2 inhibitors’ glycemic efficacy wanes as kidney function worsens. Safety results in FLOW were on par with semaglutide’s known profile in other clinical trials, Radin said. The Novo exec noted that “significantly fewer” patients in the trial’s semaglutide group experienced a serious adverse event versus the control arm. However, more patients on semaglutide discontinued therapy compared to placebo, driven by gastrointestinal disorders, which is consistent with the GLP-1 class as a whole, Radin noted. Back in March, when Novo unveiled its headline data in CKD, the company said it would file for regulatory approvals in the U.S. and Europe this year to expand semaglutide’s label. While Radin was unable to provide an update on that front, he confirmed that Novo is sticking by its plan to seek updated approvals in kidney disease by the end of 2024. Elsewhere, Novo is far from done with its semaglutide development journey. The company currently has a functional trial underway in patients with Type 2 diabetes who have peripheral arterial disease with symptomatic claudication, which is set to read out at the end of the year, Radin said. In terms of liver health, Novo is also assessing semaglutide’s potential ability to help with fibrosis in patients with fatty liver disease and steatohepatitis in a phase 3 trial. The company is testing oral semaglutide for its ability to help people with early Alzheimer’s disease as well. Novo currently has two trials underway in that space—evoke and evoke+—which are assessing semaglutide in diabetes and non-diabetes Alzheimer’s populations.  Semaglutide is currently approved in its injectable form as Ozempic for Type 2 diabetes and as Wegovy in obesity. Both medicines also boast nods for cardiovascular risk reduction. There's also an oral form of the drug called Rybelsus for diabetes.