A high blood pressure medication which was trialled by UWA has been approved for use in the United States.
The US Food and Drug Administration approval followed the PRECISION trial of aprocitentan, sold under the name Tryvio.
More than 130 million people worldwide are estimated to have a resistance to existing hypertension medication, suggesting that the relevant pathophysiological pathways have not been effectively targeted.
Lead author Professor Markus Schlaich, the Dobney Chair in Clinical Research at UWA’s Medical School, explained that the endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs.
“The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension,” he said.
“In conjunction with other medications we found the drug which targeted the endothelin pathway lowered blood pressure in patients who had resistant hypertension. Aprocitentan lowered systolic and diastolic blood pressure, and this was sustained over a period of 48-weeks supporting long-term tolerability and efficiency.”
PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia, on 730 patients, from June 2018 to April 2022.
Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic.
The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week four and from withdrawal baseline to week 40, respectively, and after four weeks of withdrawal, office systolic blood pressure significantly increased with the placebo versus aprocitentan.
The most frequent adverse event was mild-to-moderate oedema, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12·5 mg, 25 mg, and the placebo, during the 4-week double-blind element of the trial, respectively, which led to discontinuation in seven patients treated with aprocitentan.
“This is an important milestone in our fight against high blood pressure and will facilitate improved blood pressure control for many. In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week four with a sustained effect at week 40,” Professor Schlaich said.
Pharmaceutical company Idorsia plans to make Tryvio available in the US in the second half of this year to adults with resistant hypertension to be taken in combination with other antihypertensive drugs.
“We hope it will be approved and available in Australia by next year,” Professor Schlaich said.