New Drug Review: FDA Approves Tryvio for the Treatment of Hypertension in Combination With Other Antihypertensive Drugs to Lower Blood Pressure

In March 2024, the FDA approved aprocitentan (Tryvio), an endothelin receptor antagonist, for the treatment of hypertension in combination with other antihypertensive medications. The approval is specifically for lowering blood pressure in adult patients in which it is not adequately controlled by other medications.

Aprocitentan significantly reduced sitting systolic blood pressure by 3.8 mmHg more than placebo, with similar reductions in diastolic blood pressure. | image credit: sudok1 / stock.adobe.com

Efficacy

The approval of Tryvio was based on the multipart, phase 3 multicenter PRECISION study (NCT03541174), which was conducted by Idorsia Pharmaceuticals. The study had 3 parts that consisted of a 4-week double-blind period, a 32-week single-blind period, and a 12-week double-blind withdrawal period. After a 4-week placebo run-in, 730 patients were randomly assigned to receive 12.5 mg of aprocitentan, 25 mg of aprocitentan, or placebo daily for 4 weeks. All patients then received 25 mg of aprocitentan for 32 weeks, followed by a second random assignment to either 25 mg of aprocitentan or placebo for 12 weeks. The median age of participants was 63 years, with the majority being White (83%) and male (60%). The primary end point was the change in sitting systolic blood pressure (SiSBP) from baseline to week 4. Results showed that the 12.5 mg dose of aprocitentan significantly reduced SiSBP, by 3.8 mmHg more than placebo (P = .0043), with similar reductions in diastolic blood pressure. The persistence of the BP-lowering effect of aprocitentan was demonstrated in part 3 of the trial, in which patients on aprocitentan were assigned randomly to placebo or 25 mg of aprocitentan following a period during which all patients were treated with 25 mg. In patients randomly reassigned to placebo, the mean SiSBP increased, whereas in patients randomly reassigned to 25 mg of aprocitentan, the mean effect on SiSBP was maintained and was statistically superior to placebo at week 40. The treatment effect was consistent for SiSBP. Most of the BP-lowering effects occurred within the first 2 weeks of treatment.

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Safety

Approximately 30% of patients in the PRECISION study 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, 0.8% of patients experienced an adverse reaction of hypersensitivity (eg, rash, erythema, allergic edema). Common adverse reactions (≥2%) included headache, dizziness, nasopharyngitis, and fatigue. A small number of patients discontinued use due to adverse events. Aprocitentan is not recommended in patients with kidney failure (eGFR < 15mL/min) or on dialysis. Patients with renal impairment are at an increased risk of edema/fluid retention. Aprocitentan is not recommended in 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, including birth defects and fetal death. Therefore, it is important to counsel patients who can become pregnant to use acceptable methods of contraception before treatment, during treatment, and for 1 month after treatment discontinuation. Because of the risk of birth defects, aprocitentan is only available through a restricted distribution program called the TRYVIO REMS.

Dosing and Administration

Tryvio is available in tablet form, with doses of 12.5 mg and 25 mg. The 12.5-mg dose is recommended for once-daily use. The medication should be taken at the same time each day, with or without food. It is important to adhere to the prescribed dose as 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 health care provider.

To read these stories and more, download the PDF of the Drug Topics January/February issue here.

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