FDA Approves Idorsia’s Tryvio for Once-Daily Treatment of Difficult-to-Control Hypertension

Image credit: meenkulathiamma | stock.adobe.com

The FDA has approved Idorsia Ltd’s Tryvio (aprocitentan) to reduce hypertension in combination with other antihypertensive drugs in adults whose blood pressure is not adequately controlled by other therapies. Tryvio is an endothelin receptor antagonist that interferes with the binding of endothelin (ET)-1 to ETA and ETB receptors.¹

“Today, there are millions of Americans whose blood pressure is not well-controlled despite existing therapies. This is a major public health issue leading to a high incidence of cardio- and cerebrovascular events,” Jean-Paul Clozel, MD, CEO of Idorsia said in a press release. “In order to help address this issue, Idorsia developed aprocitentan, an endothelin receptor antagonist suited to the treatment of these patients. Idorsia conducted an ambitious clinical program in patients remaining hypertensive despite a minimum of three drugs at their optimal dose and sometimes up to four, five, or even six antihypertensives.”¹

Hypertension is one of the main causes of cardiovascular disease. About 10% of an estimated 1.3 billion patients with hypertension have difficult-to-control disease, even with use of multiple medications.²

Prior to the approval of Tryvio, there have been no other FDA-approved systemic antihypertensive therapies targeting the ET pathway. Currently approved medications for hypertension focus on regulation of salt and water, antagonism of the renin–angiotensin–aldosterone system, lowering the influx of extracellular calcium into the cell, sympatholytic activity, or non-selective vasodilatory effects.

The FDA based today’s approval on findings from the Phase III PRECISION trial, which analyzed the short- and long-term efficacy of Tryvio in 730 patients with difficult-to-control hypertension in a three-part study.² In the trial’s double-blind part one portion from baseline through week four, patients were randomly assigned in a 1:1:1 ratio to receive either Tryvio 12.5 mg, Tryvio 25 mg, or placebo. In the trial’s single-blind part two portion from weeks four through 36, patients from the first part who continued to part two were administered Tryvio 25 mg. In the trial’s double-blind withdrawal part three portion from weeks 36 to 48, patients were re-randomized to receive Tryvio 25 mg or placebo in a 1:1 ratio.

Tryvio achieved the trial’s primary efficacy endpoint of change in sitting systolic blood pressure (SBP), as measured by unattended automated office BP, from baseline to week four. Following week four, Tryvio significantly reduced SBP compared with placebo.

Tryvio also achieved the trial’s secondary efficacy endpoint of a sustained decline in SBP compared to placebo between weeks 36 and 40. At week 40, patients in the placebo cohort experienced an increase in SBP of +5.8 mmHg compared to Tryvio 25 mg.

The efficacy of Tryvio was consistent across multiple prespecified subgroups, including sex, age, body mass index, race, and geographic area. Treatment-emergent adverse events (AEs) in the double-blind study period occurred in 28% of the 12.5 mg cohort and 37% of the 25 mg cohort compared with 19% of patients in the placebo cohort. Mild-to-moderate fluid retention was the most frequently reported AE in patients administered Tryvio, with seven patients discontinuing therapy during the study.

“Today, we are not able to reduce blood pressure below recommended levels in at least 10% of the hypertensive patients we treat. As well, it is often patients at high risk of adverse cardiovascular outcomes and typically with comorbidities who pose this challenge,” PRECISION trial investigator Michael A. Weber, MD, professor of Medicine, Division of Cardiovascular Medicine State University of New York, said in the release. “We have had to wait for over 30 years to see the approval of an oral anti-hypertensive agent that works on a new therapeutic pathway, so Tryvio provides transformational progress in the field of systemic hypertension. It is taken as a single daily oral dose that works in combination with whatever other drugs are being prescribed and without drug-drug interactions in patients with the burden of uncontrolled hypertension. Tryvio is easy for physicians to prescribe and easy for patients to use.”¹

References

1. US FDA approves Idorsia’s once-daily TRYVIO (aprocitentan) – the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with other antihypertensives. Idorsia. News release. March 20, 2024. Accessed March 20, 2024. https://www.idorsia.com/media/news/news-archive/media-release-details?id=3195250

2. Late-Breaking Data from Pivotal Phase 3 PRECISION Study Demonstrates Significant and Sustained Effect of Aprocitentan on Lowering Blood Pressure for Patients with Difficult-to-Control Hypertension. Janssen. November 7, 2022. Accessed March 20, 2024. https://www.pharmacytimes.com/view/aprocitentan-significantly-lowers-blood-pressure-in-patients-with-difficult-to-control-hypertension