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Today, the official website of the U.S. FDA showsDeveloped jointly by Idorsia and Johnson & JohnsonTryvio (aprocitentan) oral tablets have been approved for use in combination with other antihypertensive drugs to treat adult patients with hypertension whose blood pressure cannot be adequately controlled with other medications. According to previousIdorsiaCompany Press Release,This drug is the first new mechanism-based blood pressure lowering medication approved in 30 years!

Worldwide, there are approximately 1.3 billion people with hypertension, 10% of whom, orMore than 100 million patients belong toRefractory hypertension, which means that despite receiving at least three different types of antihypertensive drugs, their blood pressure remains uncontrolled.The occurrence of hypertension is not only related to the patient's genetic predisposition, but also associated with obesity, diabetes, sedentary lifestyle, and mental stress. For patients with hypertension, the primary goal of treatment is to achieve stable and long-term blood pressure control. This is becauseLong-term uncontrolled hypertension may cause damage to the heart and blood vessels, thereby increasing the risk of heart disease, kidney failure, vascular dementia, and stroke in patients.

Aprocitentan is an orally administered dual endothelin receptor antagonistThe endothelin signaling pathway, which controls vasoconstriction, has been found to be associated with hypertensive disorders. In patients with resistant hypertension, this pathway is often found to be activated.In addition to having the potential to inhibit the endothelin pathway, Aprocitentan has a low probability of causing drug-drug interactions.These characteristics make aprocitentan a promising drug for treating patients with resistant hypertension.

Previously published clinicalPhase 3The PRECISION data analysis shows,When used in combination with other background therapies for hypertension, aprocitentan can lead to a statistically and clinically significant reduction in blood pressure in patients with resistant hypertension, which is sustained for up to 48 weeks.The trialIncluded approximately 700 patients whose seated systolic blood pressure exceeded 140 mmHg, and these patients had already received standard treatment consisting of three antihypertensive drugs.

▲AprocitentanClinical Trial Results (Image Source: Reference [2])

The PRECISION trial consists of three parts. In the first part, patients were randomly assigned to receive different doses of aprocitentan or placebo.Four weeks later, the reduction in systolic blood pressure was significantly greater in patients receiving either 12.5 mg or 25 mg of aprocitentan compared to the placebo group.Significantly higher by 3.8 mmHg (p=0.0042) and 3.7 mmHg (p=0.0046), respectively. A similar trend was observed in diastolic blood pressure, with patients receiving 12.5 mg or 25 mg of aprocitentan showing reductions in diastolic blood pressure that were 3.9 mmHg and 4.5 mmHg greater than those in the placebo group, respectively.

In the second part of the trial, all patients received 25 mg of aprocitentan for 32 weeks. The trial results showed that the reduction in systolic blood pressure was maintained in patients who received aprocitentan in the first part.Patients switching from placebo to aprocitentan treatment rapidly achieved the same degree of blood pressure reduction within 2 weeks.

In the third part of the trial, patients were re-randomized to receive either aprocitentan at a dose of 25 mg or a placebo.Four weeks later, compared with patients who continued to receive aprocitentan treatment, the systolic and diastolic blood pressure of patients receiving placebo treatment increased significantly by 5.8 mmHg (p<0.0001) and 5.2 mmHg (p<0.001), respectively.

▲Chemical structure and effects of Aprocitentan (Image source: Reference [2])

In the trial, aprocitentan also demonstrated good tolerability. The most common treatment-emergent adverse events (TEAEs) in patients were mild to moderate fluid retention, mostly manageable.

According to a meta-analysis study published in The Lancet in 2021, which included more than 300,000 people,Regardless of the participants' previous history of cardiovascular disease, a 5 mmHg reduction in systolic blood pressure leads to an approximately 10% decrease in the risk of major cardiovascular events!This has important clinical significance for hypertensive patients who already have a high risk of cardiovascular disease.

▲AprocitentanClinical Trial Safety Results (Image Source: Reference [2])

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References:

[1] Prescribing information. Retrieved March 19, 2024 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217686s000lbl.pdf

[2] The Lancet and AHA late-breaking science session reports the results of Phase 3 study of aprocitentan. Retrieved June 27, 2023, from https://www.idorsia.com/documents/com/fact-sheets-presentations/221108_aprocitentan-aha-lancet-webcast.pdf

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