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
Portopulmonary Hypertension	2
Hypertension, Pulmonary	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
California	9
Massachusetts	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

Letairis (Ambrisentan): Clinical Trials, Market Analysis, and Projections

Introduction

Letairis, also known as ambrisentan, is a selective endothelin type A receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). Here, we will delve into the clinical trials, market analysis, and projections for this drug.

Clinical Trials Overview

ATHENA-1 Study

One of the notable clinical trials for Letairis is the ATHENA-1 study. This Phase IV, randomized, double-blind, placebo-controlled trial aimed to evaluate the safety and efficacy of adding Letairis to sildenafil in patients with PAH who had a sub-optimal response to sildenafil monotherapy. The primary objective was to compare the change in pulmonary vascular resistance (PVR) after 24 weeks of treatment. The study involved 80 patients, with 40 in each arm, and also examined long-term safety and efficacy measures up to 48 weeks[1].

AMBITION Trial

The AMBITION trial is another significant study that assessed the efficacy of Letairis in combination with tadalafil. This long-term, event-driven, randomized, double-blind, active-controlled trial involved 605 treatment-naïve patients with WHO Functional Class II–III PAH. The trial demonstrated that the combination of Letairis and tadalafil reduced the risks of disease progression and hospitalization for worsening PAH, and improved exercise ability compared to monotherapy with either drug[3][4].

Mechanism of Action and Indications

Letairis works by preventing endothelin from binding to the endothelin receptor, thereby blocking the receptor-mediated vasoconstriction of vascular smooth muscle cells. It is indicated for the treatment of PAH (WHO Group 1) to improve exercise ability and delay clinical worsening. Additionally, it is approved for use in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability[2][4].

Safety Profile

The safety profile of Letairis includes potential liver injury, as evidenced by elevations in liver aminotransferases (ALT and AST). Regular monitoring of serum aminotransferase levels and bilirubin is necessary. Other side effects include decreases in hemoglobin concentration and hematocrit, and peripheral edema, which is a known class effect of endothelin receptor antagonists[1].

Market Analysis

Market Position

Despite being second to market after Tracleer (bosentan), Letairis has maintained a strong position in the PAH market. It has not exceeded the historical peak sales of Tracleer but remains a market-leading drug. The increasing adoption of endothelin receptor antagonists (ERAs) in combination with phosphodiesterase 5 (PDE5) inhibitors, as supported by the AMBITION trial, has helped sustain its market presence[2].

Generic Competition

Letairis faced generic competition in the US starting in October 2018, with other markets following shortly after. This competition has limited the drug's opportunities for further uptake within the PAH market. However, the combination therapy with tadalafil is expected to counterbalance some of the generic erosion and help maintain steady sales despite intensifying competition[2][5].

Sales Projections

The sales projections for Letairis indicate a steady but declining market share due to generic competition. According to market analyses, Letairis sales for pulmonary hypertension across the US, Japan, and five major EU markets are expected to stabilize but not grow significantly beyond 2025. The drug's sales will be influenced by the increasing use of combination therapies and the ongoing competition from generic versions[2].

Projections and Future Outlook

Combination Therapies

The future outlook for Letairis is closely tied to its use in combination with other therapies, particularly tadalafil. The AMBITION trial has established the efficacy of this combination, which is expected to continue driving the drug's market presence despite generic competition[3][4].

Generic Erosion

While generic versions of Letairis have been approved and are entering the market, the branded version is expected to maintain some market share due to its established efficacy and safety profile. However, the overall sales are projected to decline as generic alternatives become more widely available[2][5].

Patent Expiration

The patents protecting Letairis are set to expire in various countries, which will further open the market to generic competition. For instance, in the US, the generic version of ambrisentan was approved in March 2019, marking the beginning of a period of increased competition[5].

Key Takeaways

• Clinical Trials: Letairis has been evaluated in several clinical trials, including the ATHENA-1 and AMBITION studies, which have demonstrated its efficacy and safety in PAH patients.
• Market Position: Despite facing generic competition, Letairis remains a market-leading drug in the PAH market, particularly when used in combination with tadalafil.
• Safety Profile: The drug has a known safety profile that includes potential liver injury and peripheral edema.
• Sales Projections: Sales are expected to stabilize but decline due to generic competition.
• Future Outlook: The use of Letairis in combination therapies will continue to drive its market presence.

FAQs

What is Letairis used for?

Letairis is used for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability and delay clinical worsening. It is also approved for use in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH[3][4].

What are the main side effects of Letairis?

The main side effects include potential liver injury, decreases in hemoglobin concentration and hematocrit, and peripheral edema[1].

Has Letairis faced generic competition?

Yes, Letairis faced generic competition starting in October 2018 in the US, with other markets following shortly after[2][5].

What is the significance of the AMBITION trial for Letairis?

The AMBITION trial demonstrated the efficacy of Letairis in combination with tadalafil, showing reduced risks of disease progression and hospitalization for worsening PAH, and improved exercise ability[3][4].

When do the patents for Letairis expire?

The patents for Letairis are set to expire in various countries, with the US generic version approved in March 2019. The exact expiration dates vary by country[5].

Sources

1. Gilead Sciences. Gilead Initiates Letairis(R) (ambrisentan) Phase IV Program. [May 1, 2008][1].
2. PR Newswire. Letairis (ambrisentan; Gilead/GlaxoSmithKline) Market to 2025: A Selective Endothelin Type A Receptor Antagonist. [June 27, 2019][2].
3. Letairis. AMBITION Trial Design | Letairis(R) (ambrisentan). [Accessed January 1, 2025][3].
4. Letairis. Clinical Results | Letairis(R) (ambrisentan). [Accessed January 1, 2025][4].
5. DrugPatentWatch. When do the patents on LETAIRIS expire, and ... [Accessed January 1, 2025][5].