Idorsia Launches Aprocitentan (TRYVIO) in US For Treatment of Hypertension

Idorsia Pharmaceuticals U.S. Inc. has announced the availability of aprocitentan (TRYVIO™) for the US market, targeted for the treatment of hypertension, in combination with other antihypertensive drugs, to lower inadequately controlled blood pressure in adults.¹

The announcement was reported on November 15, 2024, on the opening day of the American Heart Association (AHA) Annual Scientific Sessions 2024 in Chicago, Illinois. Idorsia will present four pieces of data on aprocitentan at the meeting, including two deemed as top-scoring at the AHA’s Hypertension Scientific Sessions Specialty Conference held in September 2024.²

"Uncontrolled hypertension 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.¹ “[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."

Approximately 120 million adults in the US population experience hypertension, yet ~50% are unable to achieve blood pressure control at a target goal of <130/80 mm Hg.³ Aprocitentan, a 12.5 mg oral, once-daily medication, was approved for hypertension based on positive results from the Phase 3 PRECISION trial, according to Idorsia.¹

A 3-part trial, PRECISION randomized 730 patients with treatment-resistant hypertension, defined as the receipt of ≥3 antihypertensive drugs at baseline.⁴ Part 1 of PRECISION was a 4-week double-blind treatment period that enrolled patients 1:1:1 to receive aprocitentan 12.5 mg, aprocitentan 25 mg, or placebo. Parts 2 and 3 of PRECISION were a 32-week, single-blind period with once-daily aprocitentan 25 mg treatment and a 12-week, double-blind withdrawal period, with all patients re-randomized to aprocitentan 25 mg or placebo.

Upon analysis, at 4 weeks, aprocitentan 12.5 mg and 25 mmHg reduced in-office systolic blood pressure (SBP) by –15.4 and –15.2 mmHg from baseline, respectively, compared with –11.5 mmHg for placebo. These reductions represented differences of –3.8 mmHg (97.5% CI, –6.8 to –0.8; P =.0042) and –3.7 mmHg (97.5% CI, –6.7 to –0.8; P =.0046) versus placebo, respectively.

Further differences versus placebo were identified in the 24-hour ambulatory SBP, showing reductions of –4.2 mmHg (95% CI, –6.2 to –2.1) and –5.9 mmHg (95% CI, –7.9 to –3.8) with aprocitentan 12.5 mg and 25 mg, respectively. The most frequent adverse events identified with aprocitentan were mild-to-moderate edema or fluid retention, identified in 9% and 18% of patients receiving aprocitentan 12.5 mg and 25 mg, respectively.

In their release, Idorsia indicated aprocitentan is the only FDA-approved treatment for systemic hypertension targeting the endothelin system, a key pathway in the pathophysiology of hypertension.¹ Aprocitentan is not recommended in patients with kidney failure (eGFR <15 mL/min), as patients with renal impairment are at elevated risk of edema or fluid retention.

"Today, hypertension is the leading modifiable risk factor for cardiovascular disease and mortality in the world. [Aprocitentan’s] availability in the US is an important milestone for the millions of patients who require novel approaches to control their blood pressure,” said Tosh Butt, President and General Manager of Idorsia US.¹ “Idorsia has delivered a treatment addressing a previously unaddressed therapeutic pathway in systemic hypertension for the first time in over three decades, giving hope to patients whose existing therapies are not adequate.”

References

1. _{Idorsia. Idorsia’s once-daily tryvioTM (aprocitentan) is now available in the U.S., advancing treatment options for millions of patients with difficult-to-control hypertension. PR Newswire: press release distribution, targeting, monitoring and marketing. November 15, 2024. Accessed November 15, 2024. https://www.prnewswire.com/news-releases/idorsias-once-daily-tryvio-aprocitentan-is-now-available-in-the-us-advancing-treatment-options-for-millions-of-patients-with-difficult-to-control-hypertension-302306837.html.}
2. _{Idorsia is advancing the treatment of hypertension with new data at the 2024 American Heart Association (AHA) Scientific Sessions. Idorsia. November 11, 2024. Accessed November 15, 2024. https://www.idorsia.com/media/news/news-archive/media-release-details?id=3338042.}
3. _{Cdc. Hypertension prevalence in the U.S.: Million hearts®. Centers for Disease Control and Prevention. May 12, 2023. Accessed November 15, 2024. https://millionhearts.hhs.gov/data-reports/hypertension-prevalence.html.}
4. _{Campbell P. What to know about the APROCITENTAN approval for resistant hypertension, with Michael Weber, MD. HCP Live. April 23, 2024. Accessed November 15, 2024. https://www.hcplive.com/view/what-to-know-about-aprocitentan-for-resistant-hypertension-with-michael-weber-md.}