Positive topline results were announced from a phase 3 study evaluating aprocitentan in patients with resistant hypertension.
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. The international, multicenter, blinded, randomized PRECISION study (ClinicalTrials.gov Identifier: NCT03541174) included adults with uncontrolled blood pressure (BP) despite at least 3 background antihypertensive medications of different pharmacological classes within 1 year before screening visit.
The trial consisted of 3 sequential treatment parts. In Part 1, patients were randomly assigned 1:1:1 to receive aprocitentan 12.5mg (n=243), 25mg (n=243), or placebo (n=244) orally once daily for 4 weeks. In Part 2, all patients received aprocitentan 25mg orally once daily for 32 weeks followed by a 12-week, placebo-controlled withdrawal period (Part 3) where 614 patients were re-randomized to receive aprocitentan 25mg or placebo.
Results from Part 1 showed that treatment with aprocitentan 12.5mg and 25mg met the primary endpoint demonstrating a statistically significant and clinically meaningful reduction of systolic BP, as assessed by measurement at trough of unattended automated office BP, compared with placebo (both P <.005). In Part 2, the mean reduction in systolic BP was maintained for an additional 32 weeks in patients treated with aprocitentan during Part 1. After 4 weeks in the withdrawal period of Part 3, a significant increase in systolic BP was observed for patients in the placebo arm compared with the aprocitentan arm (P <.0001).
“The findings from this study demonstrate the crucial contributions of the endothelin pathway and highlight the enormous potential of aprocitentan to help improve blood pressure control and thereby cardiovascular outcomes in this high-risk patient cohort,” said Prof. Markus Schlaich, MD, FAHA, FESC, ISHF, The University of Western Australia, Perth, and lead investigator in the PRECISION study. “The consistency of the observations made during the study and in particular the use of the withdrawal study design after chronic use will set a new standard in the evaluation of the treatment of resistant hypertension.”
The most frequent treatment-emergent adverse event reported with aprocitentan was edema/fluid retention.
Idorsia expects to file a New Drug Application with the Food and Drug Administration (FDA) by the end of 2022.
Positive phase 3 study with aprocitentan demonstrates significant antihypertensive efficacy in patients with resistant hypertension. News release. Idorsia Pharmaceuticals Ltd. Accessed May 23, 2022. https://www.globenewswire.com/news-release/2022/05/23/2448034/0/en/Positive-Phase-3-study-with-aprocitentan-demonstrates-significant-antihypertensive-efficacy-in-patients-with-resistant-hypertension.html
This article originally appeared on MPR