Aprocitentan lowers blood pressure in resistant hypertension with obesity and across CKM stages – Idorsia

Idorsia shared positive findings from two new analyses of the pivotal Phase 3 PRECISION study of aprocitentan in patients with resistant hypertension, at the American Heart Association Hypertension Scientific Sessions 2026 on October 10th.

“For us, these results are an important step in understanding where targeting the endothelin pathway makes the greatest difference for patients with uncontrolled hypertension. In PRECISION, aprocitentan produced a double-digit blood pressure reduction in the overall population. We are encouraged to see consistent blood pressure reductions in patients with obesity and across earlier and more advanced stages of CKM, given their complex and overlapping clinical risks. Together with the reduction in UACR, stable eGFR and safety profile, this adds to the growing evidence that the endothelin pathway matters in patients across the broader spectrum of uncontrolled hypertension.” – Amer Joseph, MD, Chief Medical Officer and Head of Global Clinical Development.

An estimated 1.4 billion people worldwide live with hypertension, yet many do not achieve adequate control, increasing their risk of cardiovascular and kidney complications and premature death. The burden is particularly high among people with obesity or CKM.

A 5-10 mmHg reduction in systolic blood pressure can reduce the risk of major cardiovascular events by approximately 10%-20%. Yet, despite the well-established benefits of lowering blood pressure, many patients remain above target despite multiple therapies, underscoring the need for treatments that address additional pathways involved in hypertension.

When the endothelin system is upregulated, endothelin-1 drives vasoconstriction, vascular and cardiac hypertrophy, fibrosis, inflammation and aldosterone production. It is especially the case in populations prone to difficult-to-control hypertension such as obesity, type 2 diabetes, and renal failure. There is a strong correlation between ET-1 and markers of metabolic syndrome (body mass index, triglycerides, insulin resistance), and between ET-1 and kidney function. By blocking ETA and ETB receptors, aprocitentan targets this distinct pathway beyond the renin-angiotensin-aldosterone system.

Aprocitentan shows marked benefits in patients with obesity and hypertension

Endothelin is a driver of hypertension in individuals with obesity: A post hoc analysis of the PRECISION study. Presented by Dr Michael A Weber, MD
Markus Schlaich, Martine Clozel, Ruth Collins, Parisa Danaietash, John M. Flack, Johann Laurent, Krzysztof Narkiewicz, Ji-Guang Wang and Michael A Weber.
Abstract available online

This post hoc analysis compared 506 patients with obesity defined as body mass index ≥30 kg/m2 with 224 patients without obesity. At baseline, office blood pressure was similar between groups, while patients with obesity carried a higher burden of several comorbidities, including diabetes, chronic kidney disease, ischemic heart disease, congestive heart failure and obstructive sleep apnea.

Key findings:

– Aprocitentan 12.5 mg and 25 mg reduced office systolic blood pressure at Week 4 in patients with obesity by 15.4 and 16.0 mmHg respectively, consistent with the reduction observed in the overall PRECISION population. Double-digit absolute reductions were maintained during the 32-week single-blind treatment period to Week 36.

– Night-time ambulatory systolic blood pressure decreased in patients with obesity, with the reduction maintained during longer-term treatment.

– UACR decreased in patients with obesity, eGFR remained stable while uric acid showed favorable changes with aprocitentan versus placebo.

– Safety profile was consistent between the two cohorts

Endothelin as a therapeutic target across the cardiovascular-kidney-metabolic continuum: A post hoc analysis of the PRECISION study. Presented by Dr John M. Flack
Markus Schlaich, Martine Clozel, Parisa Danaietash, Johann Laurent, Alessandro Maresta, Krzysztof Narkiewicz, Ji-Guang Wang, Michael A Weber and John M. Flack.
Abstract available online

This post hoc analysis focused on 410 patients in CKM stage 2 and 273 patients in CKM stage 4a. Patients in stage 4a were older and had a greater burden of diabetes, chronic kidney disease, ischemic heart disease, heart failure and cerebrovascular disease, while baseline office and ambulatory blood pressure were similar between cohorts.

Key findings:

– Aprocitentan 12.5 mg reduced office systolic blood pressure at Week 4, by 15.1 mmHg in patients with CKM stage 2 and by 16.6 mmHg in those with stage 4a.

– At Week 4, daytime and night-time ambulatory systolic blood pressure decreased in both CKM cohorts.

– Increase of the UACR is associated with higher risks of mortality in patients with CKM. Aprocitentan reduced UACR by almost 50% across earlier and more advanced CKM stages in patients with albuminuria. Urate showed also favorable trends versus placebo in both CKM cohorts.

– Estimated glomerular filtration rate remained stable over the duration of the study in both cohorts. NT-proBNP was also stable, and no increase in electrolyte abnormalities was observed.

– The safety profile was consistent between CKM stages 2 and 4a.