New FDA Approval: TRYVIO™ Summary
New FDA Approval: TRYVIO™ (aprocitentan) Summary
The Food and Drug Administration (FDA) recently approved TRYVIO™ (aprocitentan) 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 medications. This is the first oral anti-hypertensive therapy which works by targeting the endothelin (ET) pathway.
Read the InpharmD summary below:
| Drug Name |
TRYVIO™ |
| Active Ingredient |
aprocitentan |
| Date of Approval |
March 19, 2024 |
| Manufacturer |
Idorsia Pharmaceuticals U.S. Inc. |
| Approval Pathways |
NDA |
| Therapeutic Class |
Antihypertensive; Endothelin Receptor Antagonist (ERA) |
| Formulation |
Tablets |
| MoA |
Aprocitentan is an ERA that inhibits the binding of endothelin (ET)-1 to ETA and ETB receptors.
ET-1, via its receptors (ETA and ETB), mediates a variety of deleterious effects such as vasoconstriction, fibrosis, cell proliferation, and inflammation. In hypertension, ET-1 can cause endothelial dysfunction, vascular hypertrophy and remodeling, sympathetic activation, and increased aldosterone synthesis. |
| Dosing and Administration |
The recommended dosage of TRYVIO™ is 12.5 mg orally once daily,
with or without food. |
| Place in Therapy |
TRYVIO™ is 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 medications. This therapy targets those whose blood pressure remains uncontrolled with existing treatments, and the clinical trial leading to TRYVIO™'s approval included patients who were on at least three antihypertensive medications.
The clinical trial was conducted in a "high-risk" population. In addition to the three antihypertensive medications, more than 60% of patients were treated with at least four drugs at screening, more than 50% had diabetes mellitus, and 20% had a history of heart failure.
TRYVIO™ is the first oral anti-hypertensive therapy which works via a new therapeutic pathway to be approved in almost 40 years. Prior to this approval, there have been no other FDA-approved systemic antihypertensive therapies targeting the endothelin (ET) pathway. Overall, this is novel therapeutic option that may be a good option in treating resistant hypertension in high-risk patients.
The main competitor for TRYVIO™ for this indication is expected to be AstraZeneca’s baxdrostat. Baxdrostat is a selective aldosterone synthase inhibitor, and is being evaluated in a Phase III BaxHTN trial (NCT06034743). The study is expected to enrol up to 720 participants with resistant hypertension taking two or more hypertensives to control their blood pressure.
Another drug in development for treating resistant hypertension is Novartis’ XXB750, a natriuretic peptide receptor 1 (NPR1) agonist. The drug is being evaluated in a Phase II trial (NCT06034743). The study is expected to enrol up to 170 participants and will be completed in September 2024. |
| Expected Market Launch Date |
Availability anticipated in 2nd half of 2024
Aprocitentan will be available in the US through a risk evaluation and mitigation strategy (REMS), due to it's boxed warning for embryo-fetal toxicity. Clinicians must enroll and complete training to be certified prescribers. Pharmacies that dispense aprocitentan must also be certified with the REMS program. |
| New Molecular Entity (NME) or Existing Formulation |
NME |
| Expected Cost |
Available only through REMS program |
| Product Discontinuation |
N/A |
| Clinical Trials |
TRYVIO™ was evaluated as a monotherapy in a Phase 2 study in patients with hypertension, and as an add-on therapy in a Phase 3 study called PRECISION in patients with confirmed resistant hypertension. In PRECISION, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4, with a sustained effect at week 40.
The PRECISION study included adults with systolic BP (SBP) 140 mmHg or greater who were on at least 3 antihypertensive medications. The trial consisted of a 4-week placebo run-in period followed by 3 parts. In part 1, patients received aprocitentan at either 12.5 mg, 25 mg, or placebo once daily during the initial 4-week treatment period. At week 4, aprocitentan 12.5 mg demonstrated statistical superiority over placebo in reducing sitting SBP (SiSBP), and this effect was consistent for sitting diastolic BP (SiDBP). After 4 weeks of treatment with aprocitentan, doses of 12.5 mg and 25 mg resulted in an approximate 4 mm Hg-reduction in office systolic blood pressure and a 5.0 mm Hg-reduction in 24-hour ambulatory systolic blood pressure, respectively, after adjusting for the change in placebo.
Edema was the most commonly reported side effect during the initial 4-week double-blind part of PRECISION, occurring in 9.1% and 18.4% of patients treated with aprocitentan 12.5 and 25 mg, respectively.
|
| Sources |
1. US FDA approves Idorsia’s once-daily TRYVIO (aprocitentan) – the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with other antihypertensives. Idorsia. News release. March 20, 2024. Accessed March 20, 2024. https://www.idorsia.com/media/news/news-archive/media-release-details?id=3195250
2. Late-Breaking Data from Pivotal Phase 3 PRECISION Study Demonstrates Significant and Sustained Effect of Aprocitentan on Lowering Blood Pressure for Patients with Difficult-to-Control Hypertension. Janssen. November 7, 2022. Accessed March 20, 2024. https://www.pharmacytimes.com/view/aprocitentan-significantly-lowers-blood-pressure-in-patients-with-difficult-to-control-hypertension
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