TheraRadar
Data updated: Jul 17, 2026

LETAIRIS (ambrisentan) · Gilead Sciences

Endothelin Receptor Antagonists Trial Activity: Declining 2 active trials
Cardiovascular Approved 2007-06-15

Letairis is an endothelin receptor antagonist indicated for the treatment of WHO Group 1 pulmonary arterial hypertension (PAH) in adult patients to improve exercise ability and delay clinical worsening. It is also indicated in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH. Clinical effectiveness was established predominantly in patients with WHO Functional Class II–III symptoms with etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%).

Source: FDA Label • Endothelin Receptor Antagonist

How LETAIRIS Works

Ambrisentan is a high-affinity, highly selective ( >4000-fold) endothelin receptor antagonist (ERA) targeting the endothelin type A (ET_A) receptor. In patients with PAH, concentrations of Endothelin-1 (ET-1)—a potent peptide that mediates vasoconstriction and cell proliferation—are significantly elevated. While ET_A receptors mediate vasoconstriction and cell proliferation, ET_B receptors are associated with vasodilation and ET-1 clearance. By selectively blocking the ET_A receptor, ambrisentan inhibits the pathogenic effects of ET-1 in the pulmonary vascular smooth muscle and endothelium.

Development Insights

Gilead Sciences conducting 4 trials (15%)
29 indications explored (Broad Platform)
pulmonary hypertension (7 trials)
pulmonary arterial hypertension (4 trials)
hypertension, pulmonary (2 trials)
3
Indications
--
Phase 3 Trials
1
Priority Reviews
19
Years on Market

Details

Status
Prescription
First Approved
2007-06-15
Patent Cliff
2031

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Routes
ORAL
Dosage Forms
TABLET

Companies

Active Ingredient: AMBRISENTAN

LETAIRIS Approval History

2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
Original
New Indication
New Form
Label Update
68 FDA actions from 2007 to 2025 · 2 indication expansions
Apr 2025 SUPPL
Update · REMS
Aug 2024 SUPPL
Update · REMS
Jun 2021 SUPPL
Update · REMS

What LETAIRIS Treats

1 indications

LETAIRIS is approved for 1 conditions since its original approval in 2007. These indications span multiple therapeutic areas including oncology, immunology, and more.

Source: FDA Label

LETAIRIS Boxed Warning

EMBRYO-FETAL TOXICITY Letairis is contraindicated for use during pregnancy because it may cause major birth defects if used by pregnant patients, based on studies in animals [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ] . Therefore, for females of reproductive potential, exclude pregnancy before the initiation of treatment with Letairis. Advise use of effective contraception before initiation, during treatment, and for one month after tre...

LETAIRIS Competitive Set

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Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.

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Clinical Trial Registry

27 trials
Trial Sponsor ID Phase Status Title
NCT07245680 COMMODITIES APHP230847 2023-509891-40-00 Ph 3 recruiting COMMODITIES Trial: Initial Dual Oral Therapy vs Monotherapy in PAH With Cardiovascular Comorbidities
NCT06256432 N-003-CRD005 Ph 2 active not recruiting Endothelin Receptor Antagonism With Ambrisentan to Treat Hepatorenal Syndrome
NCT04393246 TACTIC-E Ph 2, Ph 3 completed mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms
NCT04771000 N-003-CRD008 Ph 2 terminated A Study of Micro Dose Ambrisentan in Hospitalized Patients With Respiratory Insufficiency Due to COVID-19
NCT01342952 results posted 114588 2010-021572-29 Ph 2 completed Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
NCT05437224 AMBLE AMBEL Ph 3 completed Efficacy and Safety Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension
NCT01338636 EiPAH results posted 2008P000687 Ph 4 completed An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH)
NCT03827200 N-003-CRD003 2018-002088-25 Ph 2 terminated A Study Evaluating the Utility of Ambrisentan in Lowering Portal Pressure in Patients With Liver Cirrhosis
NCT01224210 Portopulm results posted Ambrisentan Portopulm Study Ph 3 completed Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial
NCT01051960 results posted 10-000567 Ph 4 completed Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
NCT00777920 ABS-LT results posted GS-US-300-0124 Ph 3 completed Study of Ambrisentan in Participants With Pulmonary Hypertension
NCT00840463 results posted IN-US-300-0126 Ph 4 terminated Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
NCT02290613 EDITA results posted 2014-05ED Ph 2 completed Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (SSc-APAH)
NCT02712346 Endothelin 5U01HL117684 Ph 1 completed The Role of Endothelin-1 in Sickle Cell Disease
NCT02080637 results posted Pro00050118 Ph 2 completed Ambrisentan in Single Ventricle
NCT02885012 Letairis results posted 00046009 Ph 4 terminated Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT00851929 17747 Ph 2, Ph 3 completed Ambrisentan (Letairis) for Sarcoidosis Associated Pulmonary Hypertension
NCT01971580 results posted IN-US-300-D076 Ph 4 completed The Effects of Ambrisentan on Exercise Capacity in Fontan Patients
NCT01178073 AMBITION results posted 112565 Ph 3 completed A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
NCT01808313 results posted 115812 Ph 3 completed Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)
NCT01733095 PoPH-GRZ ambrisentan Ph 1, Ph 2 withdrawn Ambrisentan for Treatment of Portopulmonary Hypertension
NCT01330108 SCOBA-PH results posted SCOBA-PH Ph 4 completed Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT00879229 ARTEMIS-PH results posted GS-US-300-0128 Ph 3 terminated ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
NCT00768300 ARTEMIS-IPF results posted GS-US-231-0101 Ph 3 terminated (ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
NCT01530464 GQ01 results posted Pro00028417 Ph 1 completed The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers
NCT01352065 ERAATH CHS-ERA-2011 Ph 2, Ph 3 completed Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
NCT00617305 ATHENA-1 results posted GS-US-300-0117 Ph 4 completed Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
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Active Pipeline

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Key Completed Trials

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Completed studies with published results, ranked by significance

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Trial Timeline

Full development history with FDA approval milestones

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Understanding FDA Approval Types
Count Type What it means
- ORIG Original approval - drug first enters market
- SUPPL - Efficacy New indication (new disease/condition approved)
- SUPPL - Labeling Label text changes (warnings, dosing updates)
- SUPPL - Manufacturing Production changes (new facility)
- SUPPL - Chemistry Formulation changes (new dosage strength)

Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.

LETAIRIS FDA Label Details

Indications & Usage

FDA Label (PDF)

Letairis is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) in adult patients: To improve exercise ability and delay clinical worsening. In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability [see Clinical Studies ]. Studies establishing effectiveness included predominantly patients with WHO Functional Class II–III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%). Letairis is an endothelin receptor antago...

⚠️ BOXED WARNING

WARNING: EMBRYO-FETAL TOXICITY Letairis is contraindicated for use during pregnancy because it may cause major birth defects if used by pregnant patients, based on studies in animals [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ] . Therefore, ...

View full patent landscape →
3 OB patents · 2 families · 77 international docs across 28 countries

LETAIRIS Patents & Exclusivity

Latest Patent: Oct 2031

Patents (3 active)

US9549926 Expires Oct 14, 2031
US9474752 Expires Dec 11, 2027
US8377933 Expires Dec 11, 2027
Source: FDA Orange Book

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Revenue Insights

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  • Historical trend analysis

Patent Timeline

  • Cliff: 2031
  • 12 active patents

Trial Analysis

  • 27 total trials
  • Stage: Declining

Competitive Landscape

  • 18 similar drugs
  • Same target/indication analysis
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Data Sources

Data sourced from official FDA and NIH databases. Click links to verify on original sources.

How We Calculate These Metrics

Trial Activity Stage

Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.

Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.

  • Growth: High proportion of early-phase trials (Phase 1/2), active development
  • Expansion: Significant Phase 3 activity, approaching or pursuing approvals
  • Mature: Substantial Phase 4 post-marketing studies
  • Stable: Mixed phase distribution, steady development
  • Declining: Low active trial ratio, reduced R&D investment