Daiichi Sankyo Company, Limited has announced the NDA submission in Japan of esaxerenone (CS-3150), a non-steroidal selective novel mineralocorticoid receptor (MR) blocker for the treatment of hypertension.

This submission is based on the results of phase 3 studies including the ESAX-HTN study in patients with essential hypertension in Japan.

Daiichi Sankyo expects esaxerenone to benefit patients and healthcare professionals in Japan by providing a new therapeutic option for the treatment of hypertension.

Esaxerenone is one of the in-licensed compounds identified during the research collaboration with Exelixis, Inc. ( Exelixis), and has subsequently been developed by Daiichi Sankyo.

Esaxerenone is an orally administered, non-steroidal, selective blocker of MR. Excess MR activation, elicited by aldosterone production triggered by the renin angiotensin system, leads to reabsorption of urinary sodium (Na+) and water by the collecting ducts in nephrons, resulting in arterial blood pressure elevation. Esaxerenone blocks MR activation and as a consequence exerts an antihypertensive effect. As recently reported, activation of MR by aldosterone or other mediators is also regarded as a potent mediator of organ damage in heart, blood vessel and kidney. Esaxerenone may therefore demonstrate an organ protective effect. The phase 3 pivotal study (ESAX-DN study) has been on-going in patients with diabetic nephropathy in Japan.

ESAX-HTN is, a 3-arm, randomized, double-blind, and parallel group comparison phase 3 study to evaluate efficacy and safety compared to eplerenone as active control in patients with essential hypertension in Japan. The primary endpoint is sitting systolic blood pressure (SBP) / diastolic blood pressure (DBP) change from baseline after 12-week treatment. 1,001 patients were randomized at 44 clinical sites in Japan. Esaxerenone 2.5mg/day showed a non-inferior antihypertensive effect to eplerenone 50mg/day in essential hypertension. There was a dose proportional antihypertensive effect between esaxerenone 2.5mg/day and 5mg/day. There were no significant safety concerns in the ESAX-HTN study.