FDA Approves Drug that Treats Hypertension in a New Way

The FDA has approved Tryvio (aprocitentan) to treat adults with uncontrolled hypertension. It is indicated to be used in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs.

Developed by Idorsia, Tryvio represents a new way to treat hypertension. It is an endothelin receptor antagonist that targets endothelin-1 A/B receptors, which is a major driver of aldosterone production. Current treatments for high blood pressure regulate salt and water (diuretics), reduce extracellular calcium (calcium channel blockers), target the renin–angiotensin–aldosterone (RAAS) system or sympatholytic activity (beta blockers, central alpha-agonist agents), or have non-selective vasodilatory effects.

Those at risk for uncontrolled hypertension include those who have sleep apnea, diabetes, obesity, chronic kidney disease, older or are Black/African American. People with uncontrolled high blood pressure are at the highest risk for stroke, heart failure, heart attack, kidney disease and vision loss. Heart disease and stroke are the leading causes of death in the United States. In 2021, hypertension was a primary or contributing cause of 691,095 deaths in the United States and costs about $131 billion each year, according to the CDC.

Tosh Butt

The recommended dosage of Tryvio is 12.5 mg orally once daily, with or without food. It will be available in the second half of 2024. The list price has not yet to be determined, but the company plans to announce the price in the coming weeks, Tosh Butt, president and general manager of Idorsia US, told Formulary Watch. “We have begun early dialogues with payers about coverage of Tryvio and these suggest an overall favorable reaction to the Tryvio clinical profile.”

During an investor presentation, Butt said payers recognize the unmet need of uncontrolled hypertension and perceive the efficacy as favorable for patients currently taking three or more medications.

Payers have suggested that Tryvio will be accessible in 2024 through the nonformulary medical exception process until the new-to-market block in Medicare and the NDC block in commercial plans are removed, Butt said during the call. He said Tryvio won’t have Medicare Part D access in 2024 or 2025, and the company will submitted Medicare Part D bids in the fourth quarter of this year for January 2026 inclusion.

The approval was based on data from a phase 3 with 730 adults with high blood pressure who were prescribed at least three antihypertensive medications. The primary efficacy endpoint was the change in sitting systolic blood pressure (SiSBP) from baseline to week four. At the end of four weeks, all patients entered the single-blind treatment period (part 2) where they received 25 mg aprocitentan once daily for 32 weeks.

Tryvio 12.5 mg was statistically superior to placebo in reducing sitting systolic blood pressure at week four. The persistence of the blood pressure-lowering effect of Tryvio was demonstrated in part three of the trial, in which patients were re-randomized to placebo or 25 mg Tryvio. In patients re-randomized to placebo, the mean sitting systolic blood pressure increased, whereas in patients re-randomized to 25 mg aprocitentan the mean effect on sitting systolic blood pressure was maintained.

The most frequent reported adverse events were edema/fluid retention and anemia. Tryvio is available through a REMS program, which includes a one-time physician and one-time pharmacist registration but no patient registration.