Idorsia Ltd. announced that further data for aprocitentan, Idorsia?s investigational dual endothelin receptor antagonist for the treatment of patients with resistant hypertension, were presented as an oral presentation entitled ?Effects of aprocitentan on blood pressure lowering and proteinuria in patients with chronic kidney disease and resistant hypertension? by George Bakris, MD, at the American Society of Nephrology (ASN) Kidney Week 2023. Patients with hypertension can often successfully control their blood pressure by combining a healthier lifestyle with effective medication.

However, approximately 10% of patients have resistant hypertension where the blood pressure remains high despite receiving at least three antihypertensive medications of different pharmacological classes, including a diuretic, at optimal doses. The Phase 3 PRECISION study demonstrated both the safety and the efficacy of aprocitentan to significantly lower blood pressure (BP) in patients with resistant hypertension on top of at least three antihypertensive medications of different classes, including a diuretic. Detailed results were published in The Lancet and presented as a Late-Breaking Science presentation during the American Heart Association (AHA) Scientific Sessions in November 2022.

More details and commentary can be found in the dedicated press release and an investor webcast featuring Prof. Markus Schlaich, an investigator in PRECISION. The presentation at ASN Kidney Week 2023 focused on the effect of aprocitentan on BP in a subgroup of 162 patients with stage 3 or 4 chronic kidney disease (CKD), defined by an estimated glomerular filtration rate (eGFR) of 15 to <60mL/min/1.73m2. The presentation included pre-specified exploratory analysis (not adjusted for multiplicity) of aprocitentan on BP measured by an automated Office BP measurement (AOBPM), and post-hoc analysis of ambulatory BP monitoring (ABPM) and urinary albumin-to-creatinine ratio (UACR) ?

a marker of kidney damage ? in this patient population. Both the 12.5 mg and 25 mg doses of aprocitentan resulted in a pronounced BP reduction from baseline to week 4 compared to placebo in patients with CKD stage 3 or 4. The mean change in office systolic BP at 4 weeks (for patients with both baseline and week 4 values) was ?13.7 mmHg for aprocitentan 12.5 mg, ?18.4 mmHg for 25 mg, and ?6.5 mmHg for placebo, for a difference versus placebo of ?7.2 mmHg and ?11.9 mmHg, respectively.

The results from ambulatory BP monitoring confirmed those derived from office measurements. The UACR at week 4, was reduced by 28% for aprocitentan 12.5 mg, 44% for aprocitentan 25 mg, and remained stable (reduction of 4%) in the placebo group. Aprocitentan was generally well tolerated; with the most common adverse events being edema/fluid retention (18% and 24% of patients receiving aprocitentan 12.5mg and 25mg, respectively, versus 2% with placebo, at week 4).

Adverse events of fluid retention and edema were primarily peripheral edema of mild intensity, mostly occurring during the first 4 to 8 weeks of treatment and were effectively managed with additional diuretic therapy. Discontinuation due to edema/fluid retention was reported for 3 out of 162 patients.