Help lower difficult-to-control hypertension by adding once-daily TRYVIO.1

TRYVIO—the first and only dual endothelin receptor antagonist for systemic hypertension—takes a different path to lower blood pressure.1,2

SEE HOW IT WORKS

TRYVIO is the first blood pressure medication to target a new pathway in more than 30 years2

Efficacy

TRYVIO significantly reduced systolic blood pressure by targeting the endothelin pathway1

In patients taking TRYVIO and at least 3 blood pressure medications (n=243), TRYVIO demonstrated statistically superior blood pressure reductions vs placebo1

Primary endpoint: change in sitting SBP (SiSBP) from baseline to week 41

Week 4 sitting trough SBP

15.4 mm Hga
97.5% CL, (-17.5, -13.3)
  • Reduction in sitting trough SBP for the placebo with antihypertensive background therapy group (n=244) was 11.6 mm Hg for a difference of 3.8 vs TRYVIO (97.5% CL, [-6.8, -0.8]; P=0.0043).1,b

aCalculated as least squares mean.1
bStatistically significant at the 2.5% level as prespecified in the testing strategy.1

Blood pressure reduction appeared consistent among subgroups defined by1:

  • Age
  • Sex
  • Race
  • BMI
  • Baseline eGFR
  • Baseline UACR
  • Medical history of diabetes
PRECISION: Study Design

A robust trial of patients taking standardized antihypertensive treatment1

The safety and efficacy of TRYVIO were evaluated in a 3-part, phase 3 multicenter study of adults (N=730) with SBP ≥140 mm Hg who were prescribed 3 or more antihypertensive medications.

  • Part 1 was 4 weeks long, double-blind, randomized, and placebo-controlled. Patients received TRYVIO 12.5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio.
  • Part 2 was 32 weeks long and single (patient)–blinded. All patients received aprocitentan 25 mg.
  • Part 3 was a 12 weeks long, double-blind, randomized, and placebo-controlled withdrawal period. Patients were re-randomized to aprocitentan 25 mg or placebo in a 1:1 ratio before part 3 began.

Primary/secondary endpoints

The primary and key secondary endpoints were changes in unattended automated office systolic blood pressure from baseline to week 4 and from week 36 to week 40, respectively.

Select inclusion criteria1,2:

  • Unattended sitting office SBP ≥140 mm Hg
  • History of uncontrolled blood pressure despite ≥3 antihypertensive medications for at least 1 year

Select exclusion criteria3:

  • Confirmed severe hypertension (grade 3)
  • Major cardiovascular, renal, or cerebrovascular medical complications in the past 6 months or NYHA stage III-IV heart failure ​
  • NT-proBNP levels ≥500 pg/mL
  • eGFR <15 mL/min/1.73 m2

At baseline, 63% of patients reported taking ≥4 antihypertensive drugs1

ARB = angiotensin II receptor blocker; BMI = body mass index; CCB = calcium channel blocker; CL = confidence limits; eGFR = estimated glomerular filtration rate; NT-proBNP = N-terminal pro-B-type natriuretic peptide; NYHA = New York Heart Association; SBP = systolic blood pressure; UACR = urine albumin-creatinine ratio.

Safety

Demonstrated long-term safety profile (48 weeks)1

The safety profile of TRYVIO was evaluated during a 
48-week study of 724 patients who had uncontrolled blood pressure (SBP ≥140 mm Hg) despite taking 3 or more antihypertensive medications.1

The most frequently reported adverse reactions to TRYVIO during the 4-week, double-blind phase of the study were edema/fluid retention and anemia.1

Adverse Reactions1,c

ADVERSE REACTION
 
Edema/fluid retention
Anemia
TRYVIO 12.5 mg
n=243
9.1%
3.7%
PLACEBO
n=242
2.1%
0

cReported with a frequency of ≥2% in TRYVIO-treated patients and greater (≥1%) than in placebo-treated patients during the initial 4-week, double-blind, placebo-controlled phase.

How it works

Takes a different path to help your patients lower their blood pressure

TRYVIO is the first and only dual ERA for the treatment of systemic hypertension.1,2

TRYVIO mechanism of action (MOA)

TRYVIO mechanism of action diagram

Hypertensive State

Overactivation of the endothelin system induces vasoconstriction and remodeling via binding of ET-1 to ETA and ETB receptors.1,4,5

The TRYVIO Effect

TRYVIO inhibits the endothelin system by blocking ETA and ETB receptors.1

The endothelin system is one of several key pathways in hypertension and has not been successfully targeted by existing systemic hypertension therapies.2,6

DOSING

Take the pressure down with once-daily dosing1

ONCE DAILY ONE 12.5-mg TABLET
  • TRYVIO may be taken with or without food.
  • Swallow tablets whole.
  • If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take two doses on the same day.
  • Initiate treatment with TRYVIO in females of reproductive potential only after confirmation of a negative pregnancy test. Patients should exclude pregnancy with negative pregnancy tests monthly during treatment and one month after discontinuation of treatment with TRYVIO.

No dose adjustment is required in patients with mild to severe renal impairment (eGFR ≥15 mL/min)1

  • TRYVIO is not recommended in patients with kidney failure (eGFR <15 mL/min) or on dialysis.
  • Patients with renal impairment are at increased risk of edema and fluid retention.

In clinical studies1,2,7,8:

  • No clinically relevant drug-drug interactions were reported.
  • No evidence of increased incidence of hyperkalemia was reported.
TRYVIO REMS

How to prescribe once-daily TRYVIO

The TRYVIO REMS is a program required by the US Food and Drug Administration (FDA) to ensure that prescribers are aware of the risk of embryo-fetal toxicity associated with TRYVIO and the need to counsel patients who can become pregnant on the actions necessary to prevent pregnancy and minimize exposure to a fetus.

All healthcare providers must enroll in the TRYVIO REMS program and comply with its requirements for prescribing TRYVIO.

Patients do NOT need to enroll in the TRYVIO REMS program, and no patient reporting is required.

To prescribe, get started in 2 steps:

STEP 1:

Complete your one-time enrollment and certification for the TRYVIO REMS program

Start REMS Enrollment

STEP 2:

Send prescription to Walgreens Specialty Pharmacy

TRYVIO is exclusively available through the Walgreens Specialty Pharmacy.

New patients starting TRYVIO are eligible for a 30-day free trial offer.a See below for details on how to prescribe.

Where to prescribe

Walgreens Specialty Pharmacy

NCPDP: 3974157

NPI# 1972560688

130 Enterprise Dr. | Pittsburgh, PA 15275

Toll Free Phone Number: 888-347-3416
Fax Number: 877-231-8302

EHR = electronic healthcare record; FDA = US Food and Drug Administration; REMS = risk evaluation and mitigation strategy.

To get a 30-day free trial, e-prescribe 2 individual prescriptions in your EHR system to Walgreens Specialty Pharmacy

PRESCRIPTION 1

The first prescription will be used to provide a 30-day free trial of TRYVIO.

PRESCRIPTION 2

While your patient begins their free trial of TRYVIO, the second prescription will be used by Walgreens to determine coverage and out-of-pocket cost.

TRYVIO Savings

Commercially eligible patients may receive TRYVIO for as little as $10 per month through Walgreens Specialty Pharmacy.b

TRYVIO Copay card

aLimitations apply. This offer is good for a 30-day (maximum 30 tablets; one time use) free trial of TRYVIO at no cost to your patient. See full Terms and Conditions.

bLimitations apply. For commercially eligible patients only. This offer is not valid under Medicare, Medicaid, or any other federal or state program. Patient must be 18 years of age or older and a resident of the United States. See full Terms and Conditions.

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INDICATION

TRYVIO is an endothelin receptor antagonist indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.

IMPORTANT SAFETY INFORMATION

WARNING: EMBRYO-FETAL TOXICITY

  • TRYVIO can cause major birth defects if used by pregnant patients.
  • In patients who can become pregnant, obtain a negative pregnancy test prior to initiation of TRYVIO and counsel patients to take monthly pregnancy tests during treatment and one month after discontinuation of TRYVIO.
  • To prevent pregnancy, patients who can become pregnant should use acceptable methods of contraception before the start of, during, and for one month after stopping treatment.
  • Because of the risk of birth defects, TRYVIO is only available through a restricted program called the TRYVIO Risk Evaluation and Mitigation Strategy (REMS).

CONTRAINDICATIONS

TRYVIO is contraindicated:

  • in pregnancy. TRYVIO can cause fetal harm when administered during pregnancy.
  • in patients who are hypersensitive to aprocitentan or any of its excipients.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity and TRYVIO REMS

Based on data from animal reproduction studies with endothelin receptor antagonists (ERAs), TRYVIO can cause fetal harm when administered during pregnancy and is contraindicated for use in patients who are pregnant. Exclude pregnancy and ensure use of acceptable contraceptive methods prior to initiation of treatment with TRYVIO. If pregnancy is detected, discontinue TRYVIO.

TRYVIO is available only through a restricted program under a REMS called the TRYVIO REMS because of the risk of embryo-fetal toxicity. Important requirements of the TRYVIO REMS include:

  • Prescribers must be certified with the TRYVIO REMS by enrolling in and completing training.
  • Pharmacies that dispense TRYVIO REMS must be certified with the TRYVIO REMS.

Further information is available at www.TRYVIOREMS.com or 1-866-429-8964.

Hepatotoxicity

Elevations of aminotransferases and hepatotoxicity are known effects of ERAs, including TRYVIO. Elevations in alanine transaminase (ALT) or aspartate aminotransferase (AST) of greater than 5-fold upper limit of normal (ULN) were observed rarely in patients treated with aprocitentan in the clinical trial, including cases with positive rechallenge. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and repeat during treatment periodically and as clinically indicated.

Do not initiate TRYVIO in patients with elevated aminotransferases (>3×ULN) or moderate to severe hepatic impairment. Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, scleral icterus, jaundice, dark urine, fever, or itching) to immediately stop treatment with TRYVIO and seek medical attention.

If sustained, unexplained, clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2×ULN, or if clinical symptoms of hepatotoxicity occur, discontinue TRYVIO.

Fluid Retention

Fluid retention and peripheral edema are known effects of ERAs, including TRYVIO. Edema/fluid retention was reported in 9% of TRYVIO-treated patients compared with 18% of patients receiving aprocitentan 25 mg (twice the recommended dose) and 2% on placebo in the clinical trial, requiring additional diuretic use in some patients. Older age and chronic kidney disease are risk factors for edema/fluid retention with TRYVIO. TRYVIO has not been studied in patients with heart failure New York Heart Association stage III-IV, unstable cardiac function, or with NTproBNP ≥500 pg/mL. TRYVIO is not recommended in these patients.

Monitor for signs and symptoms of fluid retention, weight gain, and worsening heart failure. If clinically significant fluid retention develops, treat appropriately, and consider discontinuation of TRYVIO.

Hemoglobin Decrease

Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in the clinical trial with TRYVIO. Hemoglobin decreases usually presented early, stabilized thereafter, and were reversible after discontinuation. A decrease in hemoglobin of >2 g/dL from baseline was observed in 7% of patients compared to 1% of placebo patients. A decrease to below 10.0 g/dL was observed in 3% of TRYVIO-treated patients compared to 0 patients taking placebo. Initiation of TRYVIO is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and periodically during treatment as clinically indicated.

Decreased Sperm Counts

TRYVIO, like other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility.

MOST COMMON ADVERSE REACTIONS

The most common adverse reactions (more frequent than placebo and ≥2% in TRYVIO-treated patients) are edema/fluid retention and anemia.

USE IN SPECIFIC POPULATIONS

Lactation

There are no data on the presence of aprocitentan in human milk, the effects on the breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with TRYVIO.

Renal Impairment

TRYVIO is not recommended in patients with kidney failure (eGFR<15 mL/min) or on dialysis. Patients with renal impairment are at increased risk of edema/fluid retention.

Hepatic Impairment

TRYVIO is not recommended in patients with moderate and severe hepatic impairment (Child-Pugh class B and C) because these patients may be at increased risk for poor outcomes from hepatotoxicity.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Please see full Prescribing Information including BOXED Warning and Medication Guide.

References: 1. TRYVIO™ (aprocitentan) [prescribing information]. Radnor, PA: Idorsia Pharmaceuticals US Inc; 2024. 2. Schlaich MP, Bellet M, Weber MA, et al; PRECISION investigators. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial. Lancet. 2022;400(10367):1927-1937. Published correction appears in Lancet. 2023;401(10373):268. doi:10.1016/S0140-6736(23)00119-8 3. Danaietash P, Verweij P, Wang JG, et al; PRECISION investigators. Identifying and treating resistant hypertension in PRECISION: a randomized long-term clinical trial with aprocitentan. J Clin Hypertens (Greenwich). 2022;24(7):804-813. doi:10.1111/jch.14517 4. Heidari Nejad S, Azzam O, Schlaich MP. Dual endothelin antagonism with aprocitentan as a novel therapeutic approach for resistant hypertension. Curr Hypertens Rep. 2023;25(10):343-352. doi:10.1007/s11906-023-01259-z 5. Kostov K. The causal relationship between endothelin-1 and hypertension: focusing on endothelial dysfunction, arterial stiffness, vascular remodeling, and blood pressure regulation. Life (Basel). 2021;11(9):986. doi:10.3390/life11090986 6. Clozel M. Aprocitentan and the endothelin system in resistant hypertension. Can J Physiol Pharmacol. 2022;100(7):573-583. doi:10.1139/cjpp-2022-0010 7. Schiffrin EL, Fisher NDL. Diagnosis and management of resistant hypertension. BMJ. 2024;385:e079108. Published correction appears in BMJ. 2024;385:q1430. doi:10.1136/bmj.q1430 8. Supplementary appendix to: Schlaich MP, Bellet M, Weber MA, et al; PRECISION investigators. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial. Lancet. 2022;400(10367): 1927-1937. doi:10.1016/S0140-6736(22)02034-7

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TRYVIO is an endothelin receptor antagonist indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.

WARNING: EMBRYO-FETAL TOXICITY

  • TRYVIO can cause major birth defects if used by pregnant patients.
  • In patients who can become pregnant, obtain a negative pregnancy test prior to initiation of TRYVIO and counsel patients to take monthly pregnancy tests during treatment and one month after discontinuation of TRYVIO.