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.
NCT00423592 ↗	Phase 2 Study of Ambrisentan for Liver Function Test Rescue in Pulmonary Arterial Hypertension	Completed	Gilead Sciences	Phase 2	2005-05-01	This Phase 2 study was to determine the incidence of increased serum aminotransferase concentrations (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]), as well as the overall safety and tolerability of ambrisentan, in participants with pulmonary arterial hypertension (PAH), idiopathic PAH (IPAH), or familial PAH (FPAH) who had previously discontinued ERA therapy (bosentan or sitaxsentan) due to increased serum ALT or AST concentrations.
NCT00423748 ↗	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
Systemic Sclerosis	5

Condition MeSH

Condition MeSH for AMBRISENTAN
Intervention	Trials
Hypertension	45
Pulmonary Arterial Hypertension	33
Hypertension, Pulmonary	29
Familial Primary Pulmonary Hypertension	28

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
PHASE3	1
PHASE2	1

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
Johns Hopkins University	3

Sponsor Type

Sponsor Type for AMBRISENTAN
Sponsor	Trials
Other	108
Industry	48
NIH	4

Last updated: July 26, 2026

Ambrisentan Clinical Trials Update, Market Analysis, and Exclusivity Timelines (2026 Outlook)

Ambrisentan, an endothelin receptor antagonist marketed for pulmonary arterial hypertension (PAH), has no broad late-stage (Phase 3) pipeline updates that materially change near-term competitive entry risk. Revenue is still driven by continued access in PAH and by the competitive position versus other ERA therapies and combination regimens. Patent-driven exclusivity is the primary near-to-mid term determinant of generic or biosimilar-like entry risk (for small molecules, generic pathways), with Orange Book status and any Paragraph IV litigation being the practical gating items.

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What is the latest clinical trials update for ambrisentan in PAH?

The most clinically relevant “update” for ambrisentan is not new efficacy-defining Phase 3 work, but whether new trials are changing treatment positioning (WHO functional class targeting, risk-stratification strategies, combination regimens with PDE5 inhibitors or prostacyclin pathway agents), and whether any formulation or delivery work is underway.

Are there any current Phase 3 trials for ambrisentan (2024–2026)?

No Phase 3 ambrisentan program update is established here that would justify a market-impact projection tied to new labeling. Without a confirmed Phase 3 outcome entering regulatory review, market forecasts remain driven by existing indication use, guideline adherence, and payer access rather than new clinical expansion.

What Phase 2 trials or investigator-initiated studies matter for adoption?

Ambrisentan remains part of ERA-based strategies used across PAH treatment ladders. Trial activity that changes dosing schedules, combination selection, or endpoints tied to risk assessment tends to influence clinician uptake even without label expansions.

What endpoints and populations are typically used in ambrisentan trials?

Commonly used endpoints in PAH programs include:

• 6-minute walk distance (6MWD)
• WHO functional class improvement
• time to clinical worsening (TtCW)
• hemodynamics (PVR, cardiac index)
• NT-proBNP or other risk markers (depending on era of trial)

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Which competitors does ambrisentan face in pulmonary arterial hypertension?

Ambrisentan’s competitive set is dominated by other endothelin pathway agents and commonly used PAH background therapies.

Direct ERA competitors

• Macitentan (another endothelin receptor antagonist; often preferred in formulary designs due to outcomes data and dosing convenience, depending on region)
• Bosentan (ERA with a different safety and monitoring burden)

Combination competitors

• PDE5 inhibitors (sildenafil, tadalafil)
• Soluble guanylate cyclase stimulators (riociguat where used)
• Prostacyclin pathway agents (inhaled, oral, and parenteral classes)

Where ambrisentan tends to fit clinically

Ambrisentan is typically used in combination regimens or as part of ERA-based initial therapy strategies. Market outcomes are therefore sensitive to:

• payer restrictions on ERA choice
• clinician preference based on tolerability and monitoring burden
• adherence outcomes
• patient-specific risk features

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What is the market size, revenue drivers, and demand outlook for ambrisentan?

Ambrisentan demand tracks PAH treated prevalence, guideline-driven initiation rates, and retention on therapy. Revenue is also sensitive to:

• payer formularies and step edits
• hospital procurement dynamics
• generic availability impacts (if and when exclusivity barriers fall)

Key demand drivers

• Continuing PAH diagnosis and treatment initiation
• Long-term persistence among diagnosed patients
• Use in combination regimens with PDE5 inhibitors
• Availability and reimbursement stability in major markets

Key revenue risks

• Substitution to other ERAs based on payer contracts
• Switch to lower-cost generics if ambrisentan loses exclusivity
• Label competition tied to broader outcomes claims by competitors
• Safety/tolerability events affecting persistence

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When does ambrisentan lose exclusivity and what are the generic entry risks?

For small molecules, “exclusivity” determines whether generics can enter via ANDA pathways and whether the first paragraph-IV challenger can launch at the earliest permissible date.

Orange Book status: what to check

The practical triggers for entry risk are:

• Whether the reference listed drug (RLD) has currently listed patents in the FDA Orange Book
• Whether any listed patents expire, and on what dates
• Whether any Hatch-Waxman 505(b)(2) exclusivities or non-patent exclusivity (if applicable) are still operative
• Whether any ANDA paragraph-IV litigation is ongoing and what settlement terms permit

Paragraph IV and settlement-driven launch scenarios

Entry timing typically follows one of three lanes:

1. No patent challenge: generic launch occurs at the “last patent expiry” applicable to the ANDA product.
2. Paragraph IV with sustained litigation: launch is delayed pending final court outcome.
3. Paragraph IV with settlement: launch is permitted at a negotiated date or subject to “trigger” conditions (label carve-outs, launch product terms, supply terms).

Biosimilar risk

None. Ambrisentan is a small molecule; the relevant pathway is generic substitution under ANDA, not biosimilar exclusivity.

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How strong is the ambrisentan patent estate and what patents protect the drug?

Patent strength is the business lever for generic risk. The estate can include:

• composition of matter patents (active ingredient)
• formulation patents (specific salts, polymorphs, dosage-form specifics)
• method-of-use patents (treatment regimens for PAH, combination dosing, patient-selection criteria)
• manufacturing process patents

What matters for “how strong” in practice

• The number of Orange Book-listed patents attached to the RLD
• The earliest expiry date among relevant patents
• Whether any later-expiring patents are likely to be asserted successfully in ANDA litigation
• Whether the patents are broad enough to cover generic manufacturing and labeling

What would change the competitive outcome

A favorable court stance on a later-expiring formulation or method-of-use patent can prevent launch even after earlier composition patents expire. Conversely, an early invalidation or narrow interpretation can accelerate generic readiness.

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What formulations and dosage forms of ambrisentan are protected?

Ambrisentan is marketed in oral dosage forms. Patent coverage often hinges on:

• tablet composition and excipients
• specific salt form characteristics
• manufacturing process parameters tied to stability or bioavailability
• dissolution profiles and specification windows

Why formulation patents can extend market exclusivity

If the generic ANDA requires a change that falls outside the protected formulation, it may avoid infringement. If the generic can be designed around the patent without affecting bioequivalence, litigation may shift from “does it infringe” to “is it authorized” based on Orange Book listed patents and statutory carve-outs.

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What patent litigation affects ambrisentan generic entry?

The litigation landscape determines whether generic launch is blocked, delayed, or settled.

What to track for litigation impact

• Case numbers and jurisdictions (e.g., district courts)
• Asserted Orange Book patents
• Claim construction rulings and summary judgment outcomes
• Settlement terms including allowed launch dates

Market impact logic

Even if the patents are near expiry, an ongoing litigation posture can delay launch through:

• automatic statutory stays triggered by ANDA paragraph IV filings
• negotiated “pay-for-delay” style settlements
• supply or labeling restrictions

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What is the FDA regulatory status of ambrisentan and its current label positioning?

Ambrisentan’s FDA status is anchored on its PAH indication and dosing guidance.

Mechanism-driven label utility

As an endothelin receptor antagonist, ambrisentan targets endothelin-mediated vasoconstriction and remodeling. Label positioning influences:

• who starts therapy (risk stratification)
• who is switched from alternative ERAs
• persistence and combination selection

How regulatory status affects market share

• Any label expansion or new dosing guidance would alter adoption rate.
• Any safety label tightening affects persistence and prescribing volume.

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How does ambrisentan compare with macitentan and bosentan for market performance?

Market outcomes depend on clinical differentiation and payer economics.

Efficacy and outcomes positioning

Macitentan has outcomes positioning that can favor uptake in formulary decisions. Bosentan’s monitoring burden can reduce persistence. Ambrisentan often remains competitive on clinician comfort and regimen fit, but payers can steer toward lower-cost or preferred outcome data.

Net competitive effect

• If macitentan is “preferred,” ambrisentan tends to lose new starts first.
• If generics erode price, ambrisentan can regain share through cost rather than differentiation.

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Regional market outlook: where ambrisentan is most exposed to generic entry?

The highest exposure regions are where:

• patent enforcement is weaker or timelines move faster
• generic penetration is high for PAH drugs
• procurement models prioritize lowest net cost

In most markets, timing of local marketing authorizations and regulatory review schedules determines the actual launch date after a patent barrier falls.

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Clinical trial activity vs. business impact: what should drive ambrisentan forecasts?

Forecasting ambrisentan should be anchored to:

• patent expiry and Orange Book “last patent” dates
• litigation and settlement launch dates for each challenger
• payer formulary dynamics among ERAs
• persistence and adherence changes in treated cohorts
• any label safety updates that shift net treatment costs and persistence

Without confirmed late-stage label-expanding results, clinical trial updates rarely create step-function revenue growth. They more often affect competitive positioning on adoption at the margin.

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Key Takeaways

• Ambrisentan’s near-to-mid term market trajectory is primarily determined by patent/Orange Book status and any ANDA paragraph-IV litigation or settlements rather than new Phase 3 label-changing trial results.
• Competitive pressure in PAH is strongest from macitentan and bosentan and from combination regimens that redefine first-line selection.
• Generic entry risk hinges on the “last patent expiry” concept and litigation posture, which can delay or permit market entry.
• Forecasts should model demand from treated prevalence and persistence, then apply a scenario-based price and share impact tied to generic launch timing.

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FAQs

Is ambrisentan still recommended for WHO functional class I–IV pulmonary arterial hypertension?

Clinical use follows guideline positioning and real-world risk profiles; ERA selection is typically driven by payer preference, tolerability, and persistence.

What are the main reasons patients discontinue ambrisentan?

Discontinuation risk commonly relates to tolerability, safety monitoring requirements tied to liver function, and disease progression despite therapy.

How do generic ambrisentan launches usually affect PAH treatment choices?

Generic availability typically shifts new starts toward lowest net cost while maintaining regimen selection patterns based on efficacy and tolerability.

Do ambrisentan combination regimens change market adoption?

Yes, combination choices with PDE5 inhibitors or prostacyclin pathway agents can shift where prescribers start and switch, affecting total ambrisentan throughput.

What is the most common regulatory pathway for generic versions of ambrisentan in the US?

ANDA under the Hatch-Waxman framework, with entry timing tied to Orange Book patent status and any paragraph-IV litigation or settlement stays.

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References (APA)

No sources were provided in the prompt, and no specific Orange Book listings, FDA approvals, trial registry records, or litigation dockets were included.