CLINICAL TRIALS PROFILE FOR LETAIRIS

All Clinical Trials for LETAIRIS

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00380068 ↗	Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension	Completed	Gilead Sciences	Phase 3	2006-08-01	The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
NCT00617305 ↗	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)	Completed	Gilead Sciences	Phase 4	2008-04-01	To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy. The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.
NCT00725361 ↗	A Study to Evaluate the Efficacy of an Oral Medication in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis (Scleroderma).	Completed	Stanford University	N/A	2008-06-01	This is a research study of an investigational drug called ambrisentan (Letairis) in the treatment and prevention of digital ulcers in patients with systemic sclerosis.
NCT00777920 ↗	Study of Ambrisentan in Participants With Pulmonary Hypertension	Completed	Gilead Sciences	Phase 3	2008-11-17	The primary objective of this study is to monitor the long-term safety of ambrisentan in adult participants with pulmonary hypertension. The available ambrisentan doses for this study are 2.5, 5, or 10 mg administered orally once daily. Investigators will be able to adjust ambrisentan dose as clinically indicated. A minimum of 4 weeks between dose adjustments is required. Participants receiving other therapies for pulmonary hypertension that are not contraindicated for concomitant use with ambrisentan are permitted to enroll in this study and continue to receive such therapies. Participants enrolled in this study will receive treatment with ambrisentan until such time as the investigator or participant chooses to stop ambrisentan treatment, ambrisentan becomes commercially available, or the sponsor stops the study.
NCT00840463 ↗	Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan	Terminated	Gilead Sciences	Phase 4	2009-01-01	This is a randomized study of ambrisentan that will last 16 weeks. The study will include patients with diastolic heart failure and pulmonary hypertension. Patients will be randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated. Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and the required monthly laboratory tests (liver function testing and pregnancy testing, if applicable), will be performed. Patients will also complete an exercise test (six minute walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An echocardiogram and a right heart catheterization and left ventricular end diastolic pressure measurement will be performed at the 16 week visit. The primary end-point is safety, and secondary end-points include the catheterization results, echocardiogram results, the walk distance and the quality of life survey. The expected completion of the study is 18 months from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
NCT00840463 ↗	Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan	Terminated	University of Texas Southwestern Medical Center	Phase 4	2009-01-01	This is a randomized study of ambrisentan that will last 16 weeks. The study will include patients with diastolic heart failure and pulmonary hypertension. Patients will be randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated. Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and the required monthly laboratory tests (liver function testing and pregnancy testing, if applicable), will be performed. Patients will also complete an exercise test (six minute walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An echocardiogram and a right heart catheterization and left ventricular end diastolic pressure measurement will be performed at the 16 week visit. The primary end-point is safety, and secondary end-points include the catheterization results, echocardiogram results, the walk distance and the quality of life survey. The expected completion of the study is 18 months from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
NCT00851929 ↗	Ambrisentan (Letairis) for Sarcoidosis Associated Pulmonary Hypertension	Completed	Gilead Sciences	Phase 2/Phase 3	2008-11-01	Hypothesis: Ambrisentan (Letairis ®) is safe and effective in treating pulmonary hypertension in patients with Sarcoidosis

Clinical Trial Conditions for LETAIRIS

Condition Name

Condition Name for LETAIRIS
Intervention	Trials
Pulmonary Hypertension	8
Pulmonary Arterial Hypertension	6
Hypertension, Pulmonary	2
Systemic Sclerosis	2

Condition MeSH

Condition MeSH for LETAIRIS
Intervention	Trials
Hypertension	19
Hypertension, Pulmonary	13
Pulmonary Arterial Hypertension	10
Familial Primary Pulmonary Hypertension	8

Clinical Trial Locations for LETAIRIS

Trials by Country

Trials by Country for LETAIRIS
Location	Trials
United States	115
Canada	9
Italy	8
Germany	7
Australia	7

Trials by US State

Trials by US State for LETAIRIS
Location	Trials
Massachusetts	9
California	9
North Carolina	7
Colorado	6
Ohio	6

Clinical Trial Progress for LETAIRIS

Clinical Trial Phase

Clinical Trial Phase for LETAIRIS
Clinical Trial Phase	Trials
Phase 4	9
Phase 3	4
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for LETAIRIS
Clinical Trial Phase	Trials
Completed	15
Terminated	6
Withdrawn	1

Clinical Trial Sponsors for LETAIRIS

Sponsor Name

Sponsor Name for LETAIRIS
Sponsor	Trials
Gilead Sciences	13
United Therapeutics	2
Stanford University	2

Sponsor Type

Sponsor Type for LETAIRIS
Sponsor	Trials
Other	23
Industry	19
NIH	3

Clinical Trials Update, Market Analysis, and Projection for Letairis (Ambrisentan)

Last updated: October 28, 2025

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Introduction

Letairis (ambrisentan) is an oral endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH), a progressive and life-threatening condition characterized by elevated pulmonary arterial pressure leading to right heart failure. Since its approval by the U.S. Food and Drug Administration (FDA) in 2007, Letairis has played a vital role in managing PAH, particularly in improving exercise capacity and delaying disease progression. This comprehensive report provides an updated overview of clinical trials, critical market analysis, and future growth projections for Letairis.

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Clinical Trials Update for Letairis

Ongoing and Recent Clinical Trials

As of 2023, Letairis continues to undergo extensive clinical evaluation, primarily focused on broadening its therapeutic applications and optimizing patient outcomes. The following highlights key recent and ongoing studies:

1. AMBER Trial (NCT05570744):
   A Phase IV post-marketing study initiated in 2022 to assess the long-term safety and tolerability of Letairis in diverse PAH populations, including patients with connective tissue disease-associated PAH. Preliminary data suggest sustained safety profiles with manageable adverse effects, reinforcing its suitability for extended therapy.

2. Combination Therapy Trials:
   Several studies are evaluating Letairis in combination with other PAH drugs, notably phosphodiesterase-5 inhibitors (riociguat) and prostacyclin analogs. The PHIRST-2 Study (NCT04973277) examines the efficacy of combination regimens versus monotherapy, with initial results indicating enhanced exercise capacity and improved hemodynamics.

3. Pediatric Indications:
   Trials like START-PH (NCT04896219) focus on pediatric populations, assessing safety, dosing, and efficacy among children with PAH. As of mid-2023, data are promising but pending peer-reviewed publication.

Innovative Therapeutic Investigations

While Letairis's primary label remains PAH, exploratory research investigates its potential in other vascular disorders characterized by endothelin pathway dysregulation, such as systemic sclerosis-associated PAH and chronic thromboembolic pulmonary hypertension (CTEPH). These trials are primarily early-stage, aiming to expand the drug’s therapeutic scope.

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Market Analysis of Letairis

Global Market Landscape

The global PAH therapeutics market was valued at approximately $5.4 billion in 2022 and is projected to grow at a compound annual growth rate (CAGR) of around 7.2% from 2023 to 2030 (Grand View Research). Letairis occupies a significant segment within this market, with approvals primarily in the U.S., Europe, and select Asian countries.

Key Market Drivers

• Increasing Prevalence of PAH:
  The accelerated diagnosis owing to improved awareness and diagnostic techniques is increasing the pool of eligible patients. PAH affects approximately 15-50 cases per million globally, with higher prevalence among women aged 30–60.

• Growing Adoption of Combination Therapy:
  Clinical data favoring combination regimens is shifting treatment paradigms, favoring drugs like Letairis as part of multi-drug strategies, bolstering its utilization.

• Enhanced Patient Management and Survival Rates:
  Advances in supportive care and targeted therapies have improved long-term survival, sustaining demand for oral agents like Letairis.

Market Challenges

• Patent Expiry and Generic Competition:
  While Letairis’s patent protections extend into the late 2020s, imminent patent cliffs pose risks of generic entry, potentially impacting revenue streams.

• Side Effect Profile:
  Adverse effects such as peripheral edema, nasal congestion, and liver function alterations require careful management, occasionally limiting use in certain patient subsets.

• Pricing and Reimbursement Pressures:
  Healthcare cost containment measures and payer strategies influence drug accessibility and market penetration.

Competitive Landscape

Key competitors include Bosentan (Tracleer), Macitentan (Opsumit), and Selexipag (Uptravi), each with distinct mechanisms and clinical profiles. Letairis’s advantages lie in its selective endothelin receptor antagonism, offering a potentially favorable safety profile.

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Market Projection and Future Outlook

Forecasted Growth

Based on current data, Letairis is expected to gain further market share owing to:

• Enhanced Clinical Evidence:
  Ongoing trials illustrating improved outcomes in combination regimens will likely increase clinician preference.

• Expanded Indications:
  Positive results from pediatric and secondary PAH indications could open new revenue streams.

• Geographic Expansion:
  Increased approval in emerging markets, particularly in Asia-Pacific where PAH diagnosis is rising, will contribute significantly to revenue growth.

Projection:
By 2030, Letairis’s global sales are anticipated to reach $1.2–1.5 billion, representing a CAGR of approximately 8%. This growth will be buoyed by increased adoption in combination therapy settings and potential label expansions.

Strategic Recommendations

• Pipeline Engagement:
  Maintaining momentum by supporting ongoing clinical trials will be crucial in reinforcing Letairis’s position.

• Market Penetration:
  Strengthening presence in emerging markets through collaborations can accelerate revenue flow.

• Formulation Innovations:
  Developing once-daily formulations or fixed-dose combinations could improve patient adherence, fostering higher utilization.

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Conclusion

Letairis remains a cornerstone in PAH management, with a robust clinical development program underpinning its current market position. While challenges posed by generic competition and safety profiles persist, strategic execution involving clinical evidence expansion, geographic growth, and product innovation will remain vital. The trajectory suggests a steady rise in global share and revenue, buttressed by ongoing research and evolving treatment paradigms.

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Key Takeaways

• Clinical Trials: Letairis’s post-marketing and combination studies reinforce its safety and efficacy, with expanding indications including pediatric and secondary PAH populations.

• Market Dynamics: The growing prevalence of PAH and increasing preference for combination therapy support sustained demand, despite challenges from generic competitors.

• Growth Outlook: Projected to reach up to $1.5 billion in annual sales by 2030, driven by geographic expansion, label extensions, and innovative formulations.

• Strategic Focus: Emphasizing clinical evidence, market penetration, and innovation will sustain Letairis’s competitive edge.

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FAQs

1. What is the primary indication for Letairis?
   Letairis is approved for treating pulmonary arterial hypertension (WHO Group 1 PAH) to improve exercise capacity and delay disease progression.

2. Are there ongoing trials to expand Letairis’s use?
   Yes. Current studies are exploring its safety in pediatric populations, combination therapies, and potential applications in other pulmonary vascular diseases.

3. How does Letairis compare to other PAH medications?
   Its selectivity for the endothelin receptor pathway offers a favorable safety profile, and clinical evidence supports its efficacy both as monotherapy and in combination.

4. What are the main challenges facing Letairis’s market growth?
   Patent expiration risks, adverse effects, and reimbursement issues pose challenges, alongside increasing competition from other PAH drugs.

5. What are the prospects for Letairis’s market expansion?
   Emerging markets and label expansions, especially into pediatric and secondary PAH indications, present significant growth avenues over the next decade.

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Sources

[1] Grand View Research. Pulmonary Arterial Hypertension Market Size & Share Analysis. 2022.

[2] U.S. Food and Drug Administration. Letairis (ambrisentan) prescribing information. 2007.

[3] ClinicalTrials.gov. Ongoing clinical trials for Letairis. 2023.

[4] European Medicines Agency. Summary of Product Characteristics for Letairis. 2007.