Aprocitentan (TRYVIO) has been approved by the FDA to treat hypertension in combination with other antihypertensive medications in adults who can’t adequately control their blood pressure with existing therapies, pharmaceutical company Idorsia announced in a release.1 Aprocitentan is now the first and only endothelin receptor antagonist approved for the treatment of high blood pressure.
The approval was based on data from the phase 3 PRECISION (NCT03541174) study, in which aprocitentan met both its primary and secondary endpoints. Aprocitentan demonstrated statistically significant and clinically meaningful reductions in blood pressure in combination with other standardized background antihypertensive therapies in patients with resistant hypertension over a 48 week period.2
About PRECISION
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 (PRECISION)
ClinicalTrials.gov Identifier: NCT03541174
Sponsor: Idorsia Pharmaceuticals
Summary: The goal of this clinical trial is to show the blood pressure lowering effect of aprocitentan, a new drug, when added to other anti-hypertensive drugs of patients with difficult to control (resistant) high blood pressure (hypertension), and to show that blood pressure reduction is kept for long period of time.
“The approval of TRYVIO in the US marks another major milestone for Idorsia,” Tosh Butt, president and general manager of Idorsia, said in a release.1 “With TRYVIO, we've got an innovative medicine with a unique mode of action in systemic hypertension. The team at Idorsia has a deep understanding and rich history in the field of endothelin receptor antagonism. We are eager to provide physicians and patients with a novel medicine working in a new pathway in uncontrolled hypertension that can provide additional blood pressure control.”
READ MORE: Focus On Obesity Management Before Addressing Comorbidities
PRECISION was a blinded, randomized, parallel‐group phase 3 study to assess the short‐term and sustained long‐term effects of aprocitentan on blood pressure. The study was done in 3 parts: part 1 assessed placebo-controlled efficacy of 12.5 mg and 25 mg of aprocitentan over 4 weeks, part 2 assessed the durability of 25 mg of aprocitentan for an additional 32 weeks, and part 3 was a placebo-controlled withdrawal period where patients were re-randomized to 25 mg or placebo for 12 weeks.
The primary study endpoint was the change in sitting systolic blood pressure from baseline to week 4. The secondary endpoint was the change in systolic blood pressure from week 36 to week 40.
During part 1, both 12.5 mg and 25 mg of aprocitentan demonstrated statistically significant reductions in sitting systolic blood pressure compared to placebo. In part 2, all patients treated with 25 mg of aprocitentan maintained their reductions in blood pressure and patients who switched from placebo also quickly achieved the same reduction. After 4 weeks of re-randomization (part 3), patients who received placebo saw a significant increase in systolic blood pressure compared to 25 mg of aprocitentan.
Additionally, aprocitentan was well tolerated. There were no major safety concerns in either of the dose populations. Treatment-emergent adverse events were reported in 27.6% and 36.7% of patients treated with 12.5 mg and 25 mg, respectively. Adverse events in the placebo population were reported by 19.4% of patients. The most common adverse events included edema and fluid retention.
“Today, there are millions of Americans whose blood pressure is not well-controlled despite existing therapies,” Jean-Paul Clozel, MD, CEO of Idorsia, said in a release.1 “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. I’m very proud of the Idorsia team and very happy that physicians will have a new treatment option to treat patients whose blood pressure is not controlled.”
READ MORE: Cardiology Resource Center
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. News Release. Idorsia. March 20, 2024. Accessed March 20, 2024. https://www.idorsia.com/investors/news-and-events/media-releases/media-release-details?id=3195250
2. Positive Phase 3 study with aprocitentan demonstrates significant antihypertensive efficacy in patients with resistant hypertension. News Release. Idorsia. May 23, 2022. Accessed March 20, 2024. https://www.idorsia.com/investors/news-and-events/media-releases/media-release-details?id=2758691
