The FDA has only approved aprocitentan (Tryvio; Idorsia) in the 12.5 mg dosage as the effects were similar between the 25 mg and 12.5 mg dosages.
The FDA approved aprocitentan (Tryvio; Idorsia Pharmaceuticals) for the treatment of hypertension in combination with other antihypertensive drugs to lower blood pressure in adults whose blood pressure is not adequately controlled on other medications, according to a press release.
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Aprocitentan is an endothelin (ET) receptor that inhibits binding to ET-1 to ETA and ETB receptors, which have similarities to the pathophysiology of hypertension, according to the press release. Until this approval, no other systemic antihypertensive medication targeted this pathway.
"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. 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," Jean-Paul Clozel, MD, CEO of Idorsia, said in the press release.
The drug was approved as a monotherapy in a phase 3 study for patients with hypertension and as an add on therapy in the phase 3 PRECISION (NCT03541174) study for patients with confirmed resistant hypertension. The study included individuals who had a systolic blood pressure of 140 mmHg or greater and were prescribed at least 3 antihypertensive medications. The trial included a placebo run-in period and was separated into 3 parts, according to the press release.
Trial Name: A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety
ClinicalTrials.gov ID: NCT03541174
Sponsor: Idorsia Pharmaceuticals Ltd
Completion Date: April 2022
After the 4-week placebo period, 730 individuals received randomized treatment of aprocitentan 12.5 mg, 25 mg, or the placebo once daily during the 4-week double-blind treatment period. At the end of the 4 weeks, patients entered a single-blind period where they received 25 mg of aprocitentan once daily for 32 weeks. After those 32 weeks, patients received wither 25 mg or the placebo once daily during a 12-week double blinded withdrawal period, according to the press release.
Prior to the placebo run-in period, all individuals received standard background antihypertensive therapy including an angiotensin receptor blocker, calcium channel blocker, and diuretic, which was continued through the studies. Patients who used a beta-blocker continued the treatment throughout the study as well, according to the press release.
The primary endpoint included the change in sitting systolic blood pressure from baseline to week 4 in part 1 of the study, which was measured by unattended automated office blood pressure. The key secondary endpoint included sitting systolic blood pressure from week 36, prior to randomization withdrawal to aprocitentan 25 mg or placebo in week 3, to week 40. Patients had a mean aged of 62 years and 60% were males, with 83% being White. Approximately 54% had diabetes, 31% had ischemic heart disease, and 20% had congestive heart failure. Further, approximately 63% reported taking 4 or more antihypertensive medications.
Investigators found that the 12.5 mg dosage was superior to the placebo through week 4, with the effect being consistent for sitting diastolic blood pressure. The effect continued in part 3, according to the press release. After treatment re-randomization, individuals either received the placebo or continued on 25 mg of the study drug. Those who received the placebo had an increase in mean sitting systolic blood pressure, where those receiving 25 mg of aprocitentan maintained the affect at week 40.
The results showed that most of the blood pressure lowering effect occurred within the first 2 weeks of treatment. The FDA has only approved the drug in the 12.5 mg dosage as the effects were similar between the 25 mg and 12.5 mg dosages, according to the press release.
The most frequent adverse reactions in part one of the study were edema/fluid retention and anemia.
Reference
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. News release. Idorsia. March 20, 2024. Accessed March 21, 2024. https://prnmedia.prnewswire.com/news-releases/us-fda-approves-idorsias-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-302094474.html
