FDA Approves Tryvio (aprocitentan) for Hypertension Treatment in Combination with Other Antihypertensives
核心洞察
The FDA approved aprocitentan (Tryvio) in March 2024, an endothelin receptor (搜索) antagonist, for hypertension (搜索) treatment when combined with other antihypertensive medications.
The approval was based on the Phase 3 PRECISION trial, demonstrating a significant reduction in sitting systolic blood pressure (SiSBP) compared to placebo.
Common adverse reactions in the PRECISION study included edema or fluid retention, with most cases being mild to moderate in severity.
The FDA has approved aprocitentan (Tryvio) for the treatment of hypertension (搜索) in adult patients whose blood pressure is not adequately controlled by other medications. This approval, announced in March 2024, marks a significant advancement in hypertension management, offering a new therapeutic option for patients with resistant hypertension.
Aprocitentan is an endothelin receptor (搜索) antagonist that targets a previously unaddressed pathway in the pathophysiology of hypertension (搜索). The approval was based on the results of the Phase 3 PRECISION trial (NCT03541174), a multicenter study conducted by Idorsia Pharmaceuticals (搜索). The PRECISION trial was a multipart study that included a 4-week double-blind period, a 32-week single-blind period, and a 12-week double-blind withdrawal period.
Efficacy of Aprocitentan in PRECISION Trial
The PRECISION trial enrolled 730 patients with treatment-resistant hypertension (搜索), defined as the receipt of three or more antihypertensive drugs at baseline. In the first part of the trial, patients were randomized to receive aprocitentan 12.5 mg, aprocitentan 25 mg, or placebo daily for 4 weeks. The primary endpoint was the change in sitting systolic blood pressure (SiSBP) from baseline to week 4.
Results from the PRECISION trial demonstrated that aprocitentan 12.5 mg significantly reduced SiSBP by 3.8 mmHg more than placebo (P = .0043). Similar reductions were observed in diastolic blood pressure. The persistence of the blood pressure-lowering effect was shown in the withdrawal period, where patients initially on aprocitentan and then reassigned to placebo experienced an increase in SiSBP, while those maintained on aprocitentan 25 mg maintained the effect, showing statistically superior results compared to placebo at week 40. According to Idorsia, most of the blood pressure-lowering effects occurred within the first 2 weeks of treatment.
Safety and Tolerability
In the PRECISION study, approximately 30% of patients experienced edema or fluid retention, mostly mild to moderate, with serious cases occurring in less than 1%. During the initial 4-week, double-blind, placebo-controlled treatment period, 0.8% of patients experienced hypersensitivity reactions. Common adverse reactions (≥2%) included headache, dizziness, nasopharyngitis, and fatigue. Aprocitentan is not recommended for patients with kidney failure (eGFR < 15mL/min) or those on dialysis, and caution is advised for patients with renal impairment due to an increased risk of edema/fluid retention. It is also not recommended for patients with moderate and severe hepatic impairment (Child-Pugh class B and C). Aprocitentan is contraindicated during pregnancy due to the risk of embryo-fetal toxicity, necessitating the use of contraception during treatment and for one month after discontinuation. Due to the risk of birth defects, aprocitentan is only available through the TRYVIO REMS program.
Dosing and Availability
Aprocitentan (Tryvio) is available in 12.5 mg and 25 mg tablets. The recommended dose is 12.5 mg once daily, taken at the same time each day, with or without food. Higher doses are not approved due to an increased risk of adverse effects. Discontinuation or dose adjustments should only be made under the supervision of a healthcare provider. Idorsia Pharmaceuticals (搜索) U.S. Inc. has announced the availability of aprocitentan (TRYVIO™) for the US market, targeted for the treatment of hypertension (搜索), in combination with other antihypertensive drugs, to lower inadequately controlled blood pressure in adults.
Expert Commentary
"Uncontrolled hypertension (搜索) can increase the risk of life-threatening conditions, such as major adverse cardiovascular and cerebrovascular events. For patients with comorbid conditions such as diabetes, chronic kidney disease, and heart failure, these issues pose an increased burden," said Michael A. Weber, MD, a professor of medicine in the division of cardiovascular medicine at the State University of New York. "[Aprocitentan] provides physicians with a therapeutic option targeting a previously unaddressed pathway to address the millions of patients with hypertension whose blood pressure is not adequately controlled despite being treated with the existing standards of care."