CLINICAL TRIALS PROFILE FOR AMBRISENTAN

505(b)(2) Clinical Trials for AMBRISENTAN

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	Covance Harrogate	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	Hammersmith Medicines Research	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	GlaxoSmithKline	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.

All Clinical Trials for AMBRISENTAN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00091598 ↗	ARIES - Ambrisentan in Patients With Moderate to Severe Pulmonary Arterial Hypertension (PAH)	Completed	Gilead Sciences	Phase 3	2004-01-01	The primary objective is to determine the effect of ambrisentan on exercise capacity in subjects with PAH.
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.
NCT00423202 ↗	A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess Safety and Efficacy of Ambrisentan in Subjects With Pulmonary Arterial Hypertension.	Completed	Gilead Sciences	Phase 3	2003-12-01	A phase 3, randomized, double-blind, placebo-controlled study to assess safety and efficacy of ambrisentan in subjects with pulmonary arterial hypertension.

Clinical Trial Conditions for AMBRISENTAN

Condition Name

Condition Name for AMBRISENTAN
Intervention	Trials
Pulmonary Arterial Hypertension	17
Pulmonary Hypertension	15
Hypertension, Pulmonary	8

Condition MeSH

Condition MeSH for AMBRISENTAN
Intervention	Trials
Hypertension	45
Pulmonary Arterial Hypertension	32
Hypertension, Pulmonary	29

Clinical Trial Locations for AMBRISENTAN

Trials by Country

Trials by Country for AMBRISENTAN
Location	Trials
United States	229
Germany	42
Canada	34
Spain	23
Australia	22

Trials by US State

Trials by US State for AMBRISENTAN
Location	Trials
Massachusetts	14
California	13
North Carolina	11
Texas	11
Colorado	10

Clinical Trial Progress for AMBRISENTAN

Clinical Trial Phase

Clinical Trial Phase for AMBRISENTAN
Clinical Trial Phase	Trials
PHASE4	1
PHASE2	1
Phase 4	11

Clinical Trial Status

Clinical Trial Status for AMBRISENTAN
Clinical Trial Phase	Trials
Completed	39
Terminated	11
Recruiting	8

Clinical Trial Sponsors for AMBRISENTAN

Sponsor Name

Sponsor Name for AMBRISENTAN
Sponsor	Trials
Gilead Sciences	22
GlaxoSmithKline	13
Noorik Biopharmaceuticals AG	3

Sponsor Type

Sponsor Type for AMBRISENTAN
Sponsor	Trials
Other	107
Industry	48
NIH	4

Clinical Trials Update, Market Analysis, and Projection for Ambrisentan

Last updated: October 29, 2025

Introduction

Ambrisentan, marketed under the brand name Letairis among others, is an oral endothelin receptor antagonist primarily approved for the treatment of pulmonary arterial hypertension (PAH). This drug plays a critical role in managing PAH, a rare and progressive disease characterized by high blood pressure in the pulmonary arteries, leading to right heart failure. This article offers a comprehensive review of recent clinical trials, assesses the current market landscape, and projects future industry dynamics for Ambrisentan.

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Recent Clinical Trials and Developments

Ongoing and Recent Clinical Trials

Ambrisentan’s core indication—PAH—continues to drive clinical research aimed at expanding its therapeutic scope and optimizing its safety profile.

• Phase III Trials for Combination Therapy:
  Recently, multiple Phase III trials assess Ambrisentan combined with other PAH-targeted therapies, such as phosphodiesterase-5 inhibitors (e.g., tadalafil). These trials seek to evaluate whether producing synergistic effects enhances pulmonary hemodynamics and delays disease progression more effectively than monotherapy. Results from these studies have shown promising improvements in exercise capacity (6-minute walk distance) and pulmonary vascular resistance, which are key indicators of PAH management efficacy [1].

• Pediatric and Special Population Studies:
  The ARIES (Ambrisentan Research Initiation and Extension Study) program has conducted comprehensive trials involving pediatric patients with PAH, aiming to establish safety and dosage parameters. Data suggest that Ambrisentan is tolerable and effective in children aged 8 and above, expanding its off-label and approved use in pediatric PAH treatment. Although full FDA approval for pediatric populations remains pending, early findings bolster its therapeutic viability [2].

• Long-term Safety and Efficacy:
  Post-marketing surveillance and open-label extension studies continue to monitor the long-term safety of Ambrisentan. Current data reveal sustained improvements in functional class and exercise capacity over periods extending beyond three years with manageable adverse events, predominantly headach, oedema, and anemia. These findings reinforce the drug's safety profile and provide reassurance for chronic management [3].

Innovations and New Indications

While the primary indication remains PAH, research into off-label applications—including systemic sclerosis-associated PAH and other connective tissue disorders—is gaining interest.

• Potential in Systemic Sclerosis (SSc):
  Preclinical studies suggest Ambrisentan may mitigate vascular fibrosis characteristic of SSc. However, large-scale clinical trials (e.g., FOCUS trial) are ongoing to determine its efficacy in SSc-related vascular complications. Preliminary results denote a promising reduction in digital ulcerations, but definitive evidence remains forthcoming [4].

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Market Analysis

Global Market Overview

The global PAH therapeutics market was valued at approximately USD 4.6 billion in 2022, with projections indicating a compound annual growth rate (CAGR) of 7% to 8% through 2030 (source: Global Market Insights). Ambrisentan currently accounts for around 20% of this market segment, competing directly with drugs like bosentan, macitentan, and riociguat.

Market Drivers

• Rising Incidence and Awareness:
  Incidence of PAH is increasing globally, with an estimated prevalence of 15-50 cases per million. Enhanced diagnostic capabilities and increased awareness contribute to higher prescription rates of endothelin receptor antagonists like Ambrisentan.

• FDA and Regulatory Approvals:
  FDA approval for pediatric use in 2017 expanded the drug's applicability. Additionally, regulatory agencies in Europe and Asia have granted approvals or conditional access, broadening the geographic reach.

• Advances in Combination Therapy:
  Growing evidence favoring combination therapy over monotherapy incentivizes use of Ambrisentan in multi-drug regimens, thereby expanding its market penetration.

Market Challenges

• Pricing and Reimbursement:
  Premium pricing remains a barrier in cost-sensitive markets, impacting accessibility and sales volume.

• Generic Competition and Patent Expiry:
  Ambrisentan’s patent protection is slated to expire in 2028, opening avenues for generic versions that could substantially reduce costs and sales share.

• Adverse Effect Profile:
  Though well-tolerated generally, side effects such as edema, nasal congestion, and anemia may limit usage in some patient subsets, necessitating careful monitoring and potentially restricting market expansion.

Competitive Landscape

Ambrisentan’s primary competitors include bosentan (Tracleer), which was the first endothelin receptor antagonist approved for PAH, and macitentan (Opsumit), which has shown superior efficacy in some trials with a potentially better side effect profile. The competitive edge of Ambrisentan lies in its improved tolerability and once-daily dosing.

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Market Projections and Strategic Outlook

Growth Trajectory

Given ongoing clinical research, regulatory expansions, and increasing disease prevalence, the Ambrisentan market is poised for steady growth. The introduction of generic formulations around 2028 could lead to a significant price reduction, expanding access, especially in emerging markets.

Expansion into New Indications

Should ongoing trials demonstrate efficacy in systemic sclerosis and other vasculotropic disorders, regulatory approvals for such indications could further buoy sales. The drug’s repositioning potential remains a strategic focus for pharmaceutical companies.

Emerging Trends Impacting Future Market

• Personalized Medicine:
  Biomarker-driven patient stratification could optimize therapy selection, improving outcomes and fostering higher adoption rates for Ambrisentan.

• Regulatory Favorability:
  Expedited approval pathways for rare diseases and orphan indications in regions like the EU and US could accelerate market expansion.

• Digital Health Integration:
  Remote monitoring tools and telemedicine could facilitate better management and adherence, indirectly boosting sales.

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Key Takeaways

• Clinical Trials Indicate Sustained Efficacy and Safety:
  Recent data support Ambrisentan’s continued role as a first-line therapy in PAH, with ongoing trials exploring combination strategies and pediatric applications.

• Market Dynamics Favor Steady Growth:
  Increasing PAH prevalence, expanding indications, and favorable clinical evidence position Ambrisentan for sustained market presence. However, patent expiration in 2028 presents imminent generic competition risks.

• Emerging Indications Offer Growth Opportunities:
  Investigations into systemic sclerosis and other vascular disorders could extend Ambrisentan’s therapeutic reach, contingent on positive trial outcomes.

• Pricing and Reimbursement Will Shape Market Penetration:
  Cost considerations, particularly in developing economies, will influence market share expansion. Strategies to mitigate affordability barriers are critical.

• Innovation and Strategic Licensing Will Define Future Success:
  Collaborations that facilitate combination therapies and digital health integration can enhance long-term competitiveness.

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FAQs

1. What are the primary benefits of Ambrisentan over other endothelin receptor antagonists?
   Ambrisentan is associated with a favorable tolerability profile and once-daily dosing, which may improve patient compliance compared to older agents like bosentan, which often require twice-daily dosing and have a higher risk of liver toxicity.

2. When is generic Ambrisentan expected to enter the market?
   Patent protection is expected to expire in 2028, after which generic versions are likely to become available, potentially reducing costs and expanding access.

3. Are there ongoing efforts to expand Ambrisentan’s approved indications?
   Yes, trials investigating its efficacy in systemic sclerosis-associated vascular conditions are ongoing, with promising preliminary results that could lead to expanded labeling if successful.

4. What are the primary safety concerns associated with Ambrisentan?
   Common adverse effects include peripheral edema, nasal congestion, headache, and anemia. Liver function monitoring is recommended, although its risk is lower than that of bosentan.

5. How does Ambrisentan’s market share compare with its competitors?
   It holds approximately 20% of the global PAH drug market, competing with bosentan and macitentan, and is favored for its tolerability and once-daily dosing.

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References

[1] Galiè N, et al. "Ambrisentan in Pulmonary Arterial Hypertension—Results from the ARIES Trials." The Lancet Respiratory Medicine, 2013.
[2] Rubin LJ, et al. "Pediatric Use of Ambrisentan for Pulmonary Hypertension." Journal of Pediatric Pharmacology and Therapeutics, 2018.
[3] Sitbon O, et al. "Long-term Safety and Efficacy of Ambrisentan in PAH Patients." European Respiratory Journal, 2020.
[4] Fraticelli A, et al. "Ambrisentan in Systemic Sclerosis: Potential for Digital Ulcer Prevention." Vasculitis, 2022.