Results Position Esaxerenone For Japan Diabetic Nephropathy Filing
Executive Summary
New top-line results from Japanese study set stage for submission of esaxerenone in additional high-need indication.
Daiichi Sankyo Co. Ltd.'s novel oral mineralocorticoid receptor blocker esaxerenone is positioned for an approval submission in Japan in the additional indication of diabetic nephropathy, following positive results from a pivotal Phase III trial.
The molecule, developed along with US partner Exelixis Inc. under a 2006 agreement, was launched as Minnebro in Japan in May for hypertension. Daiichi has not disclosed the exact timing of a filing in the new setting, but pointed to the medical need in Japan where diabetic nephropathy is a common complication.
It said in its recent fiscal second-quarter results that the target for a launch in the new setting is sometime in fiscal 2021 (starting April that year).
The placebo-controlled ESAX-DN trial enrolled 455 patients with incipient diabetic nephropathy taking either an angiotensin II antagonist or ACE inhibitor.
In results presented to the annual Kidney Week meeting of the American Society of Nephrology meeting, held 4-10 November in Washington, DC, Daiichi said esaxerenone (CS-3150) met its primary endpoint - the rate of remission of microalbuminuria after 52 weeks of treatment.
This was significantly higher in the treatment group, 22.1% versus 4.0% for placebo, and esaxerenone significantly reduced the urinary albumin to creatinine ratio (UACR), by 58.3% versus 8.3% for placebo.
It was also associated with a significant reduction in progression from incipient (defined as 45≤UACR<300mg/g Cr) to overt diabetic nephropathy (UACR increasing to ≥300mg/g Cr) compared with placebo (1.4% vs 7.5%), a secondary endpoint.
Hyperkalemia (high blood potassium) was observed in 8.8% of patients in the drug group, compared with 2.2% on placebo, but recovered on drug discontinuation.
Japan Medical Need
Diabetic nephropathy is one of the most common chronic complications of diabetes in Japan, where around 10 million people (some 12% of the population) are estimated to have diabetes.
Around half of all type 2 diabetics in the country develop diabetic nephropathy, which is the leading cause of moving to dialysis. The complication is currently managed mainly by use of drugs to control glucose, lipid levels and blood pressure, but the companies say this approach can be suboptimal and has an unclear effect at the later stages.
Normalization of albuminuria levels at the early stages of diabetic nephropathy can help reduce deterioration of kidney function, where the use of esaxerenone can help reduce levels of aldosterone, a main mediator in organ damage, and stimulate sodium absorption into the kidney.
Under the Exelixis alliance, Daiichi is solely responsible for the development and commercialization of the molecule and will pay commercialization milestones and "low double-digit" sales royalties to its US partner.
Esaxerenone is currently under development only in Japan and not for any other indications.