Bosentan - Generic Drug Details

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

Bosentan is the generic ingredient in two branded drugs marketed by Natco Pharma Ltd, Actelion, Alembic, Alvogen Pine Brook, Amneal Pharms Co, Chartwell Molecular, Hikma, Mylan, Ph Health, Sun Pharm, Watson Labs Inc, and Zydus Pharms, and is included in fourteen NDAs. There are two patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.

Bosentan has twenty-eight patent family members in twenty-three countries.

There are nineteen drug master file entries for bosentan. Six suppliers are listed for this compound. There are two tentative approvals for this compound.

Summary for bosentan

International Patents:	28
US Patents:	2
Tradenames:	2
Applicants:	12
NDAs:	14
Drug Master File Entries:	19
Finished Product Suppliers / Packagers:	6
Raw Ingredient (Bulk) Api Vendors:	85
Clinical Trials:	136
Patent Applications:	7,827
Drug Prices:	Drug price trends for bosentan
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for bosentan
What excipients (inactive ingredients) are in bosentan?	bosentan excipients list
DailyMed Link:	bosentan at DailyMed

See drug prices for bosentan

Recent Clinical Trials for bosentan

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

Sponsor	Phase
Assistance Publique - Hpitaux de Paris	PHASE2
Boehringer Ingelheim	PHASE1
University of Edinburgh	PHASE2

See all bosentan clinical trials

Generic filers with tentative approvals for BOSENTAN

Applicant	Application No.	Strength	Dosage Form
		125MG	TABLET;ORAL
		62.5MG	TABLET;ORAL
		32MG	TABLET;ORAL

The 'tentative' approval signifies that the product meets all FDA standards for marketing, and, but for the patents / regulatory protections, it would approved.

Pharmacology for bosentan

Drug Class	Endothelin Receptor Antagonist
Mechanism of Action	Cytochrome P450 2C9 Inducers Cytochrome P450 3A Inducers Endothelin Receptor Antagonists

Anatomical Therapeutic Chemical (ATC) Classes for bosentan

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

Paragraph IV (Patent) Challenges for BOSENTAN

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
TRACLEER	for Oral Suspension	bosentan	32 mg	209279	1	2019-02-08

US Patents and Regulatory Information for bosentan

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Alvogen Pine Brook	BOSENTAN	bosentan	TABLET;ORAL	206002-001	Apr 26, 2019		DISCN	No	No
Watson Labs Inc	BOSENTAN	bosentan	TABLET;ORAL	207110-002	Apr 26, 2019	AB	RX	No	No
Actelion	TRACLEER	bosentan	TABLET, FOR SUSPENSION;ORAL	209279-001	Sep 5, 2017	AB	RX	Yes	Yes	8,309,126		Y
Amneal Pharms Co	BOSENTAN	bosentan	TABLET;ORAL	209742-002	Apr 26, 2019		DISCN	No	No
Actelion	TRACLEER	bosentan	TABLET;ORAL	021290-002	Nov 20, 2001	AB	RX	Yes	Yes
Actelion	TRACLEER	bosentan	TABLET, FOR SUSPENSION;ORAL	209279-001	Sep 5, 2017	AB	RX	Yes	Yes	7,959,945		Y
Hikma	BOSENTAN	bosentan	TABLET;ORAL	208695-002	Apr 26, 2019		DISCN	No	No

Expired US Patents for bosentan

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Actelion	TRACLEER	bosentan	TABLET;ORAL	021290-001	Nov 20, 2001	5,292,740
Actelion	TRACLEER	bosentan	TABLET;ORAL	021290-002	Nov 20, 2001	5,292,740

EU/EMA Drug Approvals for bosentan

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Janssen-Cilag International N.V.	Tracleer	bosentan	EMEA/H/C/000401Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III.Efficacy has been shown in:, , , Primary (idiopathic and familial) PAH;, PAH secondary to scleroderma without significant interstitial pulmonary disease;, PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger's physiology., , , Some improvements have also been shown in patients with PAH WHO functional class II., , Tracleer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.,	Authorised	no	no	no	2002-05-14

International Patents for bosentan

Country	Patent Number	Title	Estimated Expiration
Mexico	2007014454	TABLETA DE BOSENTAN DISPERSABLE. (DISPERSIBLE BOSERTAN TABLET.)
Australia	2006248593	Dispersible bosertan tablet
Portugal	1883397
China	101175484	Dispersible bosertan tablet
Poland	1883397
Russian Federation	2007146395	ДИСПЕРГИРУЕМЫЕ ТАБЛЕТКИ БОЗЕНТАНА
Slovenia	1883397

Supplementary Protection Certificates for bosentan

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0526708	C300097	Netherlands		PRODUCT NAME: BOSENTAN, DESGEWENST IN DE VORM VAN EEN ZOUT OF EEN HYDRAAT OF IN DE VORM VAN EEN ESTER VAN DE HYDROXYLGROEP VAN DE 2-HYDROXYETHOXY REST MET EEN ZUUR MET DE FORMULE R5-OH, WAARIN R5 EEN C1-7-ALKANOYL, BENZOYL, OF HETEROCYCLYCARBONYL VOORSTELT; NATL. REGISTRATION NO/DATE: U/1/02/220/001 - 005 20020515; FIRST REGISTRATION: CH IKS 58841 01 - 02 20020228
0526708	0290017-3	Sweden		PRODUCT NAME: BOSENTAN ELLER ETT SALT DAERAV; NAT. REGISTZRATION NO/DATE: EU/1/02/220/001 20020515; FIRST REGISTRATION: CH 55841 01 20020228
0526708	SPC/GB02/030	United Kingdom		PRODUCT NAME: BOSENTAN 4-(1,1-DIMETHYLETHYL)-N-(6-(2-HYDROXYETHOXY)-5-(2-METHOXYPHENOXY)-2(PYRIMIDIN-2-YL)PYRIMIDIN-4-YL)BENZENESULFONAMIDE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
0526708	02C0042	France		PRODUCT NAME: BOSENTAN MONOHYDRATE; NAT. REGISTRATION NO/DATE: EU/1/02/220/001 20020515; FIRST REGISTRATION: LI - 55841 20020228

Market Dynamics and Financial Trajectory for Bosentan

Last updated: November 26, 2025

Executive Summary

Bosentan, marketed primarily under the brand name Tracleer, is a dual endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH). Since its approval in 2001, Bosentan has carved a significant niche within the orphan drug market, driven by its unique mechanism, expanding indications, and evolving regulatory environment. This analysis explores the current market landscape, key drivers influencing its financial trajectory, competitive positioning, and future growth prospects. The comprehensive review provides actionable insights for stakeholders in the pharmaceutical industry and investors seeking strategic entry points.

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What Is Bosentan and How Does It Work?

Bosentan's pharmacology involves antagonism of endothelin-1 receptors (ET_A and ET_B), reducing vasoconstriction and proliferation in pulmonary vasculature. Its primary indication, pulmonary arterial hypertension, involves elevated pulmonary artery pressures, which lead to right heart failure if untreated.

• Approved Indication: PAH (FDA, EMA, and other regulators)
• Off-Label/Investigational Uses: Scleroderma-related PAH, digital ulcers (exploratory)
• Mechanism: Dual receptor blockade — impacts vasoconstriction, proliferation, and fibrosis pathways

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Current Market Landscape

Global Sales and Market Share

Parameter	2022 (Estimated)	2023 (Forecasted)	Notes
Global Bosentan Market Revenue	~$1.4 billion	~$1.5 billion	Slight growth driven by increased prevalence and diagnosis rates
Market Share in PAH Drugs	~15%	Stable	Competed mainly by ERAs (Endothelin Receptor Antagonists) such as Ambrisentan and Macitentan
Key Regional Markets	North America (~50%), Europe (~25%), Asia-Pacific (~20%), Rest of World (~5%)	-	North America remains dominant

Key Clinics and Patient Demographics

• Prevalence: Estimated 15–50 cases per million in developed countries
• Patient Population: Primarily females, aged 30-60 years
• Treatment Penetration: Under 70% of diagnosed patients receive PAH-specific therapy

Competitive Overview

Drug	Approval Year	Sales (2022)	Advantages	Limitations
Bosentan (Tracleer)	2001 (FDA)	~$1.4 billion	First oral PAH drug, evidence-supported	Hepatotoxicity risk, drug interactions
Ambrisentan	2007	~$700 million	Fewer liver issues, once-daily dosing	Less comprehensive data in certain subsets
Macitentan	2013	~$850 million	Longer half-life, improved safety profile	Higher cost

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Market Dynamics: Key Drivers & Challenges

Drivers

1. Growing Prevalence of PAH

   • Incidence rising due to better detection, aging populations, and increased awareness.
   • Research indicates a 4% annual increase in PAH diagnoses globally.

2. Expanded Indications & Unmet Medical Needs

   • Extension to other forms of pulmonary hypertension (e.g., CTD-PAH, CTEPH after surgery) fuels demand.
   • Regulatory agencies (FDA, EMA) have recently approved additional pediatric and orphan indications.

3. Pipeline and Combination Therapy Approvals

   • Shift toward combination therapy strategies enhances Bosentan’s utilization.
   • Recent approvals include bosentan in combination with PDE-5 inhibitors and prostanoids.

4. Pricing and Reimbursement Policies

   • Reimbursement negotiations, especially in Europe and North America, influence market penetration.
   • Orphan drug status confers pricing premiums in several jurisdictions.

Challenges

1. Safety Profile & Side Effects

   • Hepatotoxicity and teratogenic risks necessitate regular liver function monitoring.
   • These safety concerns impose operational costs and limit patient adherence.

2. Competition from Superior Agents

   • Macitentan’s longer half-life and improved safety profile threaten Bosentan’s market share.
   • Oral formulations of newer agents with fewer side effects emerging as preferred options.

3. Pricing Pressures & Patent Expiry

   • Patent life nearing end or already expired in certain markets opens generic competition.
   • Cost containment policies pressure pricing strategies.

4. Regulatory & Policy Shifts

   • Stricter reimbursement standards, especially under health technology assessments (HTA) regimes (e.g., NICE, ICER).
   • Focus on cost-effectiveness may limit premium pricing.

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Financial Trajectory Insights

Revenue Trends and Forecasts

Year	Global Sales (USD billion)	Growth Rate	Comments
2020	~$1.2 billion	N/A	Stable demand amid COVID-19 pandemic
2021	~$1.3 billion	+8%	Recovery and increased diagnosis rates
2022	~$1.4 billion	+7%	Market expansion, new regional launches
2023f	~$1.5 billion	+7%	Slight increase expected from pipeline and expanded indications

Cost Drivers and Pricing Strategy

Factor	Impact
Manufacturing Costs	Stable, with economies of scale
R&D Investments	Especially for pipeline and safety studies
Regulatory Compliance	Increasing costs for post-market surveillance
Reimbursement & Pricing	Negotiations impacting net revenue

Patent & Market Exclusivity

• Patent Status: Patents expiring between 2024–2025 in major markets; generic entries imminent.
• Regulatory Data Exclusivity: Typically 10 years, supporting revenue till approx. 2030 in key markets.

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Competitive Analysis

Agent	Strengths	Weaknesses	Market Position
Bosentan	First oral PAH, extensive clinical data	Safety concerns, drug-drug interactions	Stable, mature drug with moderate growth prospects
Ambrisentan	Fewer side effects, once daily dosing	Limited data in certain advanced PAH populations	Growing share, positioned as safer alternative
Macitentan	Longer half-life, better safety profile	Higher cost, newer entrant	Increasing market penetration, particularly in Europe
Riociguat (Adempas)	Different mechanism, effective in CTEPH	Newer agent, safety profile different	Niche position, expanding indications

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Future Growth Opportunities

Expansion into Adjacent Markets

• Rare Pulmonary Hypertension Subtypes: Scleroderma-associated PAH and connective tissue disease-related cases.
• Combination Therapies and Personalized Medicine: Utilizing biomarker-driven approaches.
• Emerging Regions: Asia-Pacific markets exhibit underpenetration, offering growth potential.

Pipeline and Regulatory Outlook

• Next-generation Endothelin Receptor Antagonists: Research into more selective agents with fewer side effects.
• Biosimilars and Generics: Entry post-patent expiry could impact revenue but may also reduce treatment costs, broadening accessibility.

Policy & Reimbursement Environment

Region	Policies Impacting Market	Opportunities
North America	CMS reimbursement policies favoring cost-effective therapies	Strategic pricing and partnerships
Europe	HTA assessments regulate pricing; Orphan designation favorable	Market access strategies for niche indications
Asia-Pacific	Rapid healthcare infrastructure expansion and rising expenditure	Local partnerships and tailored pricing strategies

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Comparative Review: Bosentan vs. Competitors

Parameter	Bosentan	Macitentan	Ambrisentan
Approval Year	2001	2013	2007
Half-life	5 hours	13 hours	9 hours
Administration	Twice daily	Once daily	Once daily
Liver Toxicity Risk	Higher	Lower	Lower
Efficacy Data	Robust, long-term data	Similar efficacy, better safety	Similar efficacy, fewer side effects

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Key Regulatory and Policy Frameworks

• FDA (U.S.): Orphan Drug Designation (2001), Post-marketing surveillance required.
• EMA (Europe): Orphan status, Pediatric Investigation Plans (PIPs).
• Pediatric Use: Regulatory incentives for pediatric studies, potentially expanding label indications.
• Pricing & Reimbursement: Vary across regions; managed through health technology assessments (HTAs).

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Key Takeaways

• Market Maturity and Patent Expiry: The imminent expiration of key patents in 2024–2025 requires strategic planning for biosimilars and generics to mitigate revenue erosion.
• Driving Factors for Growth: Increasing PAH awareness, expanded indications, and combination therapies potentiate moderate growth (~7% CAGR expected till 2025).
• Competitive Landscape: Bosentan maintains relevance due to robust clinical data and early market entry, but faces challenges from newer agents with improved safety profiles.
• Pricing and Reimbursement Trends: Emphasis on cost-effectiveness may pressure margins, requiring innovative market access strategies.
• Emerging Opportunities: Focus on orphan indications, regional market expansion, and pipeline development essential for sustained financial performance.

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FAQs

Q1: How will patent expiration influence Bosentan's market share?
Patent expirations in many regions are expected in 2024–2025. This will likely introduce biosimilar and generic competition, reducing prices and current revenues. Strategic adaptations, such as expanding indications and penetrating emerging markets, are critical to offset revenue decline.

Q2: Are newer endothelin receptor antagonists likely to replace Bosentan?
While agents like Macitentan and Ambrisentan offer improved safety profiles, Bosentan’s established efficacy and data robustness sustain its market position. Replacement depends on safety, cost, and regional healthcare policies, but it is expected that Bosentan will remain relevant during the patent transition period.

Q3: What are the primary safety concerns limiting Bosentan's usage?
Hepatotoxicity and teratogenicity necessitate regular liver monitoring and contraceptive use. These safety risks increase operational costs and can restrict use in specific patient populations.

Q4: How significant is the role of combination therapy in Bosentan's future?
Combination therapy is increasingly standard for PAH management. Bosentan’s compatibility with PDE-5 inhibitors enhances its use. Regulatory approvals of combination protocols further bolster its market access.

Q5: Which emerging regions present lucrative growth opportunities?
Asia-Pacific, especially China, India, and Southeast Asia, exhibits rising disease prevalence and improving healthcare infrastructure, offering substantial growth potential for Bosentan through strategic regional partnerships.

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References

1. [1] Galiè et al., “2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension,” European Heart Journal, 2016.
2. [2] FDA, “Tracleer (Bosentan) Label,” 2022.
3. [3] IQVIA, “Pharmaceutical Market Reports,” 2022.
4. [4] European Medicines Agency, “Assessment Report for Bosentan,” 2001.
5. [5] Global Pulmonary Hypertension Market Analysis, MarketResearch.com, 2022.

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In conclusion, Bosentan remains a key player within the PAH therapeutic landscape, with steady growth prospects driven by regional expansions, pipeline developments, and evolving treatment paradigms. Stakeholders should proactively manage impending patent cliffs and safety considerations to sustain its financial trajectory.