Aprocitentan found efficacious in patients with resistant hypertension in Phase 3 study

Aprocitentan is an investigational, oral, dual endothelin receptor antagonist designed to potently inhibit the binding of endothelin-1 (ET-1) to ETA and ETB receptors. A phase 3 study has revealed positive topline results evaluating aprocitentan in patients with resistant hypertension.

Positive top-line results of PRECISION, the Phase 3 study investigating aprocitentan for the treatment of patients of resistant hypertension were announced by Idorsia.

Aprocitentan significantly reduced blood pressure when added to standardized combination background antihypertensive therapy in patients with resistant hypertension over 48 weeks of treatment.

Hypertension is one of the most common cardiovascular risk factors, and its prevalence continues to rise. According to a recent study, there are more than one billion people living with hypertension worldwide-a number which has almost doubled in the past 40 years.1

While many patients with hypertension are successfully treated with various existing anti-hypertensive therapies, 10–20% of the hypertensive population have blood pressure that remains high despite receiving at least three antihypertensive medications of different pharmacological classes, including a diuretic, at optimal doses, and they are categorized in hypertension guidelines2,3,4 and in the medical community as having resistant hypertension.

Certain populations are at a particular high risk of developing resistant hypertension later in life; these include patients with a high body mass index (BMI), African Americans, post-menopausal women and patients with obstructive sleep apnea.5,6,7

It is estimated that by 2025, there could be approximately 10 million patients in the US who could be classified as having resistant hypertension and a similar number of patients in Europe.3,4,8 Uncontrolled hypertension can lead to multiple cardiovascular and renal adverse outcomes, including stroke, heart disease, and kidney failure. These co-morbidities increase a patient's vulnerability and the complexity of their treatment.9,10,11

Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented:

"I have long been convinced that resistant hypertension is only resistant to treatment because the endothelin system had not been tackled. The observation of high endothelin levels in populations most at risk of developing resistant hypertension, as well as the close association between endothelin and the comorbidities often seen in patients with resistant hypertension, suggested that endothelin is a key contributor to the problem. I believe the top-line results from PRECISION support our initial hypothesis that endothelin is the missing link when hypertension is not adequately controlled with existing therapies."

Reference:

Bin Zhou, et al. The Lancet; 2017; 389(10064):37-55, R.M. Carey, et al. Hypertension, 2018; 72, pp. e53-e90, Noubiap, J. J., et al., Heart 2019; 105:98-105. Carey RM, et al. Hypertension. 2019; 73(2):424-431. Coylewright, M., et al. Hypertension, 2008; 51, 952-9. Roberie, D. R., et al. Curr Opin Cardiol, 2012; 27, 386-91. Khan, A., et al. Int J Hypertens, 2013; 193010-193010. Lu Y, et al. Hypertension. 2022; 79(1):207-217. Daugherty, S. L., et al. Circulation. 2012; 125(13):1635-42. Kumbhani, D. J., et al. Eur Heart J. 2013; 34(16):1204-14 Muntner, P., et al. Hypertension. 2014; 64:1012–1021