ALLSCHWIL, Switzerland — October 12, 2026
Idorsia Ltd. reported positive findings from two post-hoc analyses of its Phase 3 PRECISION study evaluating aprocitentan in patients with resistant hypertension, including individuals with obesity and those across the cardiovascular-kidney-metabolic (CKM) disease continuum. Presented at the American Heart Association (AHA) Hypertension Scientific Sessions 2026 on October 10, the analyses showed substantial reductions in blood pressure alongside favorable changes in urinary albumin-to-creatinine ratio (UACR) and stable estimated glomerular filtration rate (eGFR). In patients with obesity, aprocitentan 12.5 mg and 25 mg reduced office systolic blood pressure by 15.4 mmHg and 16.0 mmHg, respectively, at Week 4. In patients across CKM stages 2 and 4a, the 12.5 mg dose reduced office systolic blood pressure by 15.1 mmHg and 16.6 mmHg, respectively. The findings reinforce the potential role of endothelin receptor blockade as an additional approach for difficult-to-control hypertension, particularly among patients with overlapping metabolic and kidney-related risk factors. However, the subgroup analyses were post hoc, and the reported kidney-related findings should be interpreted as exploratory rather than proof of kidney protection.
Aprocitentan Reduces Blood Pressure in Patients With Obesity
The first analysis examined 506 patients with obesity and 224 patients without obesity who participated in the PRECISION study. Obesity was defined as a body mass index of at least 30 kg/m². Although baseline office blood pressure was similar between the groups, patients with obesity had a greater burden of comorbidities, including diabetes, chronic kidney disease, ischemic heart disease, congestive heart failure and obstructive sleep apnea. At Week 4, aprocitentan 12.5 mg and 25 mg produced office systolic blood pressure reductions of 15.4 mmHg and 16.0 mmHg, respectively, in patients with obesity. Double-digit reductions were maintained during the 32-week single-blind treatment period through Week 36. Night-time ambulatory systolic blood pressure also decreased, with reductions sustained during longer-term treatment. Investigators additionally reported a decrease in UACR, stable eGFR and favorable changes in uric acid. The safety profile was consistent between the obesity and non-obesity cohorts. These findings are relevant because obesity frequently coexists with resistant hypertension and other cardiometabolic conditions, creating additional challenges in achieving blood pressure control despite multiple medications.
CKM Analysis Shows Consistent Effects Across Disease Stages
The second post-hoc analysis evaluated aprocitentan in 410 patients with CKM stage 2 and 273 patients with CKM stage 4a, representing different points along the cardiovascular-kidney-metabolic disease continuum. Patients in stage 4a were older and had a greater burden of diabetes, chronic kidney disease, ischemic heart disease, heart failure and cerebrovascular disease, although baseline office and ambulatory blood pressure levels were similar between the cohorts. At Week 4, aprocitentan 12.5 mg reduced office systolic blood pressure by 15.1 mmHg in CKM stage 2 and 16.6 mmHg in CKM stage 4a. Daytime and night-time ambulatory systolic blood pressure also decreased in both groups. Among patients with albuminuria, UACR declined by approximately 50% across the two CKM stages. Estimated glomerular filtration rate remained stable during the study, while NT-proBNP levels were stable and no increase in electrolyte abnormalities was observed. Favorable trends in uric acid were also reported compared with placebo. These results suggest that the blood pressure-lowering effect was consistent across the evaluated disease stages. Nevertheless, the subgroup findings do not establish that aprocitentan prevents kidney failure or cardiovascular events, and further evidence is needed to determine the clinical significance of the observed biomarker changes.
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Endothelin Pathway Targeting Expands Hypertension Treatment Evidence
Aprocitentan is an oral, once-daily dual endothelin receptor antagonist that blocks the binding of endothelin-1 to ETA and ETB receptors. Endothelin-1 contributes to vasoconstriction and is implicated in vascular remodeling, inflammation and processes associated with difficult-to-control hypertension. By targeting this pathway, aprocitentan acts through a mechanism distinct from commonly used antihypertensive approaches that target the renin-angiotensin-aldosterone system. The PRECISION trial was a multicenter Phase 3 study involving patients whose systolic blood pressure remained elevated despite standardized treatment with three antihypertensive medications, including a diuretic. Aprocitentan is approved in the United States as TRYVIO for use with other antihypertensive drugs in adults whose blood pressure is inadequately controlled on other medications. It is also approved as JERAYGO in the European Union, the United Kingdom, Switzerland and Canada for resistant hypertension in combination with other antihypertensives. The new analyses add subgroup evidence supporting its blood pressure-lowering activity in patients with obesity and across selected CKM stages. Further studies will be important to establish whether the favorable UACR and other biomarker changes translate into meaningful long-term kidney and cardiovascular benefits.
Source:: Idorsia press release
