AMBRISENTAN - Generic Drug Details

What are the generic sources for ambrisentan and what is the scope of freedom to operate?

Ambrisentan is the generic ingredient in two branded drugs marketed by Apotex, Aurobindo Pharma, Cipla, Mylan, Ph Health, Sigmapharm Labs Llc, Sun Pharm, Watson Labs Inc, Zydus Pharms, and Gilead, and is included in ten NDAs. There are three patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Ambrisentan has fifty-one patent family members in twenty-six countries.

There are nine drug master file entries for ambrisentan. Thirteen suppliers are listed for this compound.

Summary for AMBRISENTAN

International Patents:	51
US Patents:	3
Tradenames:	2
Applicants:	10
NDAs:	10
Drug Master File Entries:	9
Finished Product Suppliers / Packagers:	13
Raw Ingredient (Bulk) Api Vendors:	72
Clinical Trials:	69
Patent Applications:	5,377
Drug Prices:	Drug price trends for AMBRISENTAN
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for AMBRISENTAN
What excipients (inactive ingredients) are in AMBRISENTAN?	AMBRISENTAN excipients list
DailyMed Link:	AMBRISENTAN at DailyMed

See drug prices for AMBRISENTAN

Recent Clinical Trials for AMBRISENTAN

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
The First Hospital of Jilin University	PHASE4
Nanjing First Hospital, Nanjing Medical University	NA
Ningbo Medical Center Lihuili Hospital	NA

See all AMBRISENTAN clinical trials

Pharmacology for AMBRISENTAN

Drug Class	Endothelin Receptor Antagonist
Mechanism of Action	Endothelin Receptor Antagonists

Anatomical Therapeutic Chemical (ATC) Classes for AMBRISENTAN

C02KX	Antihypertensives for pulmonary arterial hypertension
C02K	OTHER ANTIHYPERTENSIVES
C02	ANTIHYPERTENSIVES
C	Cardiovascular system

Paragraph IV (Patent) Challenges for AMBRISENTAN

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
LETAIRIS	Tablets	ambrisentan	5 mg and 10 mg	022081	1	2015-02-09

US Patents and Regulatory Information for AMBRISENTAN

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Sun Pharm	AMBRISENTAN	ambrisentan	TABLET;ORAL	210784-001	Mar 28, 2019	AB	RX	No	No
Watson Labs Inc	AMBRISENTAN	ambrisentan	TABLET;ORAL	208252-001	Mar 28, 2019	AB	RX	No	No
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-002	Jun 15, 2007	AB	RX	Yes	Yes	8,377,933
Sigmapharm Labs Llc	AMBRISENTAN	ambrisentan	TABLET;ORAL	208354-001	Apr 10, 2019	AB	RX	No	No
Mylan	AMBRISENTAN	ambrisentan	TABLET;ORAL	208441-002	Mar 28, 2019	AB	RX	No	No
Apotex	AMBRISENTAN	ambrisentan	TABLET;ORAL	210701-001	May 19, 2022	AB	RX	No	No

Expired US Patents for AMBRISENTAN

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-002	Jun 15, 2007	5,932,730
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-002	Jun 15, 2007	5,703,017
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-002	Jun 15, 2007	7,109,205
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-001	Jun 15, 2007	7,601,730
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-001	Jun 15, 2007	5,703,017
Gilead	LETAIRIS	ambrisentan	TABLET;ORAL	022081-002	Jun 15, 2007	8,349,843

EU/EMA Drug Approvals for AMBRISENTAN

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
GlaxoSmithKline (Ireland) Limited	Volibris	ambrisentan	EMEA/H/C/000839Volibris is indicated for treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III, including use in combination treatment (see section 5.1).  Efficacy has been shown in idiopathic PAH (IPAH) and in PAH associated with connective tissue disease.Volibris is indicated for treatment of PAH in adolescents and children (aged 8 to less than 18 years) of WHO Functional Class (FC) II to III including use in combination treatment. Efficacy has been shown in IPAH, familial, corrected congenital and in PAH associated with connective tissue disease (see section 5.1).	Authorised	no	no	no	2008-04-20
Mylan S.A.S	Ambrisentan Mylan	ambrisentan	EMEA/H/C/004985Ambrisentan Mylan is indicated for the treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III, including use in combination treatment. Efficacy has been shown in idiopathic PAH (IPAH) and in PAH associated with connective tissue disease.Ambrisentan Mylan is indicated for the treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III, including use in combination treatment. Efficacy has been shown in idiopathic PAH (IPAH) and in PAH associated with connective tissue disease.	Authorised	yes	no	no	2019-06-20

International Patents for AMBRISENTAN

Country	Patent Number	Title	Estimated Expiration
Spain	2627944
Hong Kong	1218393	用於治療肺高壓的複合物 (COMPOSITION FOR TREATING A PULMONARY HYPERTENSION)
Eurasian Patent Organization	201390428	КОМПОЗИЦИИ И СПОСОБЫ ЛЕЧЕНИЯ ЛЕГОЧНОЙ ГИПЕРТЕНЗИИ
Hungary	S1600027
Lithuania	2637664
European Patent Office	2952193	COMPOSITION DE TRAITEMENT DE L'HYPERTENSION PULMONAIRE (COMPOSITION FOR TREATING A PULMONARY HYPERTENSION)

Supplementary Protection Certificates for AMBRISENTAN

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2101777	122016000039	Germany		PRODUCT NAME: AMBRISENTAN IN VERWENDUNG IN DER KOMBINATIONSTHERAPIE MIT TADALAFIL; REGISTRATION NO/DATE: EU/1/08/451 20151120
0785926	08C0041	France		PRODUCT NAME: AMBRISENTAN; REGISTRATION NO/DATE: EU/1/08/451/001-004 20080421
2101777	C20160017 00199	Estonia		PRODUCT NAME: AMBRISENTAAN;REG NO/DATE: EU/1/08/451 25.11.2015
2101777	300813	Netherlands		PRODUCT NAME: AMBRISENTAN TOEGEPAST IN COMBINATIEBEHANDELING MET TADALAFIL; REGISTRATION NO/DATE: EU/1/08/451 (C(2008) 1637) 20151125
2101777	93081	Luxembourg		PRODUCT NAME: AMBRISENTAN UTILISE EN TRAITEMENT COMBINE AVEC TADALAFIL; FRIST REGISTRATION: 20151125
2101777	CA 2016 00024	Denmark		PRODUCT NAME: AMBRISENTAN USED IN COMBINATION TREATMENT WITH TADALAFIL; REG. NO/DATE: EU/1/08/451 (001-004) 20151125

Market Dynamics and Financial Trajectory for Ambrisentan

Last updated: July 27, 2025

Introduction

Ambrisentan, marketed under the brand name Letairis among others, is a selective endothelin receptor antagonist primarily approved for the treatment of pulmonary arterial hypertension (PAH). Since its approval, Ambrisentan has established itself within a niche but growing therapeutic market. Its dynamics are shaped by regulatory, clinical, competitive, and economic factors, influencing its market positioning and financial prospects.

Pharmacological Profile and Therapeutic Indication

Ambrisentan functions by blocking endothelin-1, a potent vasoconstrictor implicated in PAH pathophysiology. Approved by the U.S. Food and Drug Administration (FDA) in 2007, it offers a targeted approach with demonstrated efficacy in improving exercise capacity and delaying disease progression in PAH patients. Its safety profile, characterized by risks such as peripheral edema and hepatotoxicity, aligns with other drugs in its class (e.g., bosentan, macitentan), but with a favorable selectivity profile that has influenced prescribing patterns.

Market Dynamics

Growth Drivers

1. Increasing Prevalence of PAH:
   The global prevalence of PAH is estimated at 15-50 cases per million inhabitants, with higher incidences among females and certain genetic predispositions. With advancements in diagnostics, early detection has increased, expanding the eligible patient population for Ambrisentan.

2. Expanding Treatment Guidelines:
   Recommendations increasingly favor endothelin receptor antagonists (ERAs) as first-line therapy, especially in combination regimens, promoting sustained demand for drugs like Ambrisentan. The 2022 ESC/ERS guidelines endorse ERAs, reinforcing its market position.

3. Growing Awareness and Diagnosis:
   Enhanced clinician awareness, coupled with improved diagnostic tools such as echocardiography and right heart catheterization, boosts prescription rates of targeted therapies.

4. Combination Therapy Acceptance:
   Ambrisentan’s compatibility with phosphodiesterase-5 inhibitors and prostacyclin analogs enables its integration into combination regimens, which are associated with better clinical outcomes and are favored in both guidelines and payer systems.

Market Limiters

1. Biomarker Limits and Patient Stratification:
   Identification of responders versus non-responders remains challenging; this uncertainty may restrict utilization in certain populations.

2. Safety and Side Effect Concerns:
   The risks of hepatotoxicity and potential teratogenicity necessitate stringent monitoring, possibly limiting physical and geographic patient access.

3. Pricing and Reimbursement Challenges:
   As patent protections mature, generic formulations and biosimilars could erode market share. Payer restrictions based on cost-effectiveness thresholds also impact sales.

4. Competition Within Class:
   Other ERAs such as bosentan and macitentan have comparable efficacy and safety profiles. Market share shifts depend heavily on physician preference, formulary access, and pricing strategies.

Financial Trajectory

Revenue Trends and Forecasts

• Historical Performance:
  Since its launch, Ambrisentan has experienced steady growth driven by increasing prevalence and adoption in PAH management. Global sales reached approximately $600 million in 2022, with North America comprising roughly 50% of this revenue, reflecting high penetration rates and reimbursement coverage.

• Regional Variations:
  North America remains the largest market due to advanced healthcare infrastructure and regulatory approvals. European markets are also significant, with a growing foothold in Asia-Pacific driven by expanding healthcare access.

• Projection Outlook:
  Analysts project a compounded annual growth rate (CAGR) of 4-6% over the next five years, driven by increasing diagnosis and combination therapy use. Patent expirations in select markets from 2025 onward could suppress revenues unless offset by biosimilar entrants or alternative formulations.

R&D and Pipeline Influence

• Pipeline Developments:
  While no direct chemical modifications or new indications have currently been announced, pipeline candidates aiming for better safety profiles or novel mechanisms may influence future positioning.

• Regulatory Changes:
  Approval of generic or biosimilar versions could significantly reduce pricing power, influencing the upward revenue trajectory.

Competitive Landscape

Ambrisentan faces competition primarily from bosentan (Tracleer) and macitentan (Opsumit), both of which possess similar efficacy with differing safety profiles and dosing regimens. The competitive edge of Ambrisentan lies in its selective receptor targeting, which reduces certain adverse effects, but cost considerations and clinician familiarity heavily influence market share.

Regulatory Environment and Its Impact

Regulatory bodies have implemented strict monitoring programs and risk evaluation mitigation strategies (REMS), especially for teratogenic effects, impacting prescribing flexibility. These regulatory constraints influence market dynamics by necessitating adherence to comprehensive monitoring, which can raise healthcare costs and affect patient access.

Economic and Market Challenges

• Pricing Pressures:
  Increasing prevalence algorithms and competitive pricing from generics will compel manufacturers to optimize pricing strategies.

• Healthcare Policy Impact:
  Cost-effectiveness analyses and value-based pricing models are expected to shape payer coverage decisions.

• Emerging Technologies:
  The development of novel therapies, such as prostacyclin receptor antagonists and gene therapies, could disrupt the existing PAH treatment paradigm, with potential implications on Ambrisentan's market share.

Conclusion and Future Outlook

Ambrisentan’s market trajectory is poised for moderate growth, buoyed by increasing disease awareness and evolving treatment landscapes favoring targeted therapies. Nonetheless, generics, competitive ERAs, and regulatory challenges constitute potential headwinds. The company's strategic focus on demonstrating real-world efficacy, safety, and cost-effectiveness will be essential for maintaining and expanding its market position.

---

Key Takeaways

• Growing Prevalence and Better Diagnostics drive demand, supporting steady revenue growth for Ambrisentan over the next five years.
• Combination Therapy adoption enhances its clinical utility and market penetration.
• Patent expirations and the introduction of biosimilars could pressure prices, requiring strategic pricing and marketing to preserve margins.
• Competitive ERAs and emerging therapies necessitate ongoing innovation and clinical differentiation.
• Regulatory and reimbursement policies significantly influence access and profitability, emphasizing the need for continuous compliance and value demonstration.

---

FAQs

1. What are the primary advantages of Ambrisentan over other ERAs?
Ambrisentan's selectivity for endothelin-a receptors offers a favorable safety profile, especially reduced hepatotoxicity compared to bosentan, and less frequent dosing, improving patient adherence.

2. How will patent expirations affect Ambrisentan’s market share?
Patent cliffs could lead to generic entries, significantly reducing prices and revenues unless the manufacturer secures new patents or develops next-generation formulations.

3. What are the main safety concerns associated with Ambrisentan?
Hepatotoxicity and teratogenic risk necessitate regular liver function monitoring and strict pregnancy prevention programs, impacting prescribing patterns and patient compliance.

4. How is combination therapy influencing Ambrisentan’s market?
Its compatibility with other PAH drugs promotes its role in multifaceted treatment regimens, enhancing its outlook amid guidelines favoring combination approaches.

5. What emerging factors could reshape Ambrisentan’s market?
Advances in gene therapy, novel drug classes, and more personalized medicine approaches could reduce reliance on current ERAs, altering long-term market dynamics.

---

Sources

1. [1] U.S. Food and Drug Administration. Letairis (Ambrisentan) Prescribing Information.
2. [2] European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, 2022.
3. [3] IQVIA, Global Pulmonary Hypertension Market Data, 2022.
4. [4] EvaluatePharma, Market Outlook for Pulmonary Hypertension Drugs, 2023.
5. [5] Drug Patent & Market Exclusivity Data, Drugs.com, 2023.