Macitentan; tadalafil - Generic Drug Details

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

Macitentan; tadalafil is the generic ingredient in one branded drug marketed by Actelion and is included in one NDA. There are three patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Macitentan; tadalafil has ninety-nine patent family members in thirty-four countries.

One supplier is listed for this compound.

Summary for macitentan; tadalafil

International Patents:	99
US Patents:	3
Tradenames:	1
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Clinical Trials:	10
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for macitentan; tadalafil
DailyMed Link:	macitentan; tadalafil at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for macitentan; tadalafil

Constraining patent/regulatory exclusivity:

CHRONIC TREATMENT OF ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH, WHO GROUP I AND WHO FUNCTIONAL CLASS (FC) II-III)

Dosage:

TABLET;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for macitentan; tadalafil

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

Sponsor	Phase
Humanis Saglık Anonim Sirketi	PHASE1
Janssen Research & Development, LLC	Phase 1
Covance	Phase 3

See all macitentan; tadalafil clinical trials

Pharmacology for macitentan; tadalafil

Drug Class	Endothelin Receptor Antagonist Phosphodiesterase 5 Inhibitor
Mechanism of Action	Endothelin Receptor Antagonists Phosphodiesterase 5 Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for macitentan; tadalafil

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

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

G04BE	Drugs used in erectile dysfunction
G04B	UROLOGICALS
G04	UROLOGICALS
G	Genito-urinary system and sex hormones

US Patents and Regulatory Information for macitentan; tadalafil

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-002	Mar 22, 2024		RX	Yes	Yes
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-002	Mar 22, 2024		RX	Yes	Yes
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-002	Mar 22, 2024		RX	Yes	Yes	7,094,781*PED				Y
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-001	Mar 22, 2024		RX	Yes	No	7,094,781*PED				Y
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-002	Mar 22, 2024		RX	Yes	Yes	10,946,015*PED				Y
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-002	Mar 22, 2024		RX	Yes	Yes
Actelion	OPSYNVI	macitentan; tadalafil	TABLET;ORAL	218490-001	Mar 22, 2024		RX	Yes	No

International Patents for macitentan; tadalafil

Country	Patent Number	Title	Estimated Expiration
Russian Federation	2009111378
Poland	2059246
European Patent Office	1693372
Netherlands	300672
South Korea	101313395
Denmark	1928409
Hong Kong	1133597

Supplementary Protection Certificates for macitentan; tadalafil

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1345920	132014902244514	Italy		PRODUCT NAME: MACITENTAN(OPSUMIT); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/13/893/001-002, 20131220
2059246	CA 2024 00050	Denmark		PRODUCT NAME: KOMBINATION AF (A) MACITENTAN ELLER ET FARMACEUTISK ACCEPTABELT SALT DERAF OG (B) TADALAFIL ELLER ET FAR-MACEUTISK ACCEPTABELT SALT DERAF; REG. NO/DATE: EU/1/24/1859 20240930
2059246	832	Finland
1345920	CR 2014 00012	Denmark		PRODUCT NAME: MACITENTAN OG FARMACEUTISK ACCEPTABLE SALTE HERAF; REG. NO/DATE: EU/1/13/893 20131227
1345920	300672	Netherlands		PRODUCT NAME: MACITENTAN, DESGEWENST IN DE VORM VAN EEN FARMACEUTISCH AANVAARDBAAR ZOUT; REGISTRATION NO/DATE: EU/1/13/893/001-003 20131220
1345920	CA 2014 00012	Denmark		PRODUCT NAME: MACITENTAN OG FARMACEUTISK ACCEPTABLE SALTE HERAF; REG. NO/DATE: EU/1/13/893 20131220
2059246	LUC00371	Luxembourg		PRODUCT NAME: A COMBINATION OF (A) MACITENTAN OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND (B) TADALAFIL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF; AUTHORISATION NUMBER AND DATE: EU/1/24/1859 20240930

Market Dynamics and Financial Trajectory for Macitentan and Tadalafil

Last updated: July 28, 2025

Introduction

The pharmaceutical landscape for endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors has seen significant innovation and competition, particularly with the introduction and evolving market presence of macitentan and tadalafil. These drugs, each addressing different but sometimes overlapping therapeutic areas, exhibit unique market dynamics influenced by scientific advancements, regulatory pathways, pricing strategies, and clinical benchmarks. This analysis delineates the current and forecasted financial trajectories for macitentan and tadalafil, emphasizing market drivers, challenges, and opportunities.

Product Profiles and Therapeutic Areas

Macitentan, developed by Actelion Pharmaceuticals (a subset of Johnson & Johnson), is an endothelin receptor antagonist primarily indicated for pulmonary arterial hypertension (PAH). Approved by the FDA in 2013, it offers a once-daily oral regimen demonstrating improved efficacy and safety profiles over earlier agents like bosentan. Its mechanism involves vasodilation of pulmonary arteries, making it a cornerstone in PAH management.

Tadalafil, developed by Eli Lilly, is a PDE5 inhibitor with broad therapeutic applications. It initially gained US FDA approval in 2003 for erectile dysfunction (ED), later expanding into benign prostatic hyperplasia (BPH) and pulmonary arterial hypertension (PAH) under different formulations and dosing regimens. Tadalafil’s longer half-life (up to 17.5 hours) facilitates flexible dosing, supporting its popularity in multiple indications.

Market Dynamics

1. Competitive Landscape and Market Share

Macitentan

Since its launch, macitentan has effectively competed with alternative PAH therapies like bosentan, ambrisentan, and newer agents such as Riociguat. Its improved safety profile, particularly reduced hepatotoxicity and favorable oral bioavailability, has strengthened its market position[^1].

Global PAH treatment markets are expanding, driven by aging populations, increased diagnosis, and innovative therapies. The global pulmonary arterial hypertension drugs market is projected to reach USD 6.12 billion by 2027, with endothelin receptor antagonists comprising a significant share[^2].

Tadalafil

Tadalafil dominates the ED market with a substantial share owing to its long-acting profile and efficacy. Its versatility extends to BPH and PAH, contributing to diversified revenue streams. The ED segment alone is projected to be valued at over USD 8 billion by the mid-2020s, with tadalafil maintaining a leading position among PDE5 inhibitors[^3].

Its generic availability post-patent expiry in many jurisdictions has further driven penetration, though branded formulations still command premium pricing in certain regions.

2. Regulatory and Approval Pathways

Macitentan secured swift regulatory approval driven by its demonstrated safety and efficacy in PAH. Ongoing investigations into expanded indications could propel future market growth, contingent on approval.

Tadalafil's multiple approvals across indications facilitate access across diverse markets, supporting consistent revenue streams. Regulatory adaptations in emerging markets also contribute positively.

3. Pricing Strategies and Reimbursement

Pricing remains a critical differentiator. Macitentan’s pricing correlates with its innovative edge and clinical benefits; however, cost pressures in healthcare systems necessitate value-based pricing strategies. Tadalafil benefits from a well-established generic market, leading to lower prices and broad accessibility, though patent expirations pose revenue challenges for branded formulations.

In key markets such as the U.S. and Europe, reimbursement policies significantly impact adoption rates. Success hinges on demonstrating clinical value and cost-effectiveness.

4. Market Drivers

• Increasing prevalence of PAH and other indications.
• Diagnostic advancements enabling earlier detection and treatment initiation.
• Patient preference for convenient oral therapies.
• Strong clinical trial data supporting efficacy and safety.
• Expanding geographic reach, especially into emerging markets where healthcare infrastructure improves.

5. Challenges and Market Barriers

• High drug development costs and lengthy approval processes delay revenue streams.
• Pricing pressures from payers and regulators constrain profit margins.
• Generic competition for tadalafil reduces revenue in mature markets.
• Limited pipeline breakthroughs may impede long-term growth unless driven by novel formulations or indications.

Financial Trajectory and Market Forecasts

Macitentan

Since its 2013 introduction, macitentan’s sales momentum has grown steadily. By 2021, global sales surpassed USD 430 million[^4]. Forecasts suggest this figure could reach USD 700 million by 2025, driven by:

• Expanded indications, including potential roles in portal hypertension and other vascular disorders.
• Growing awareness and diagnosis of PAH globally.
• Strategic partnerships and regional market growth, particularly in Asia-Pacific and Latin America.

However, competition from new agents and biosimilars may temper growth, emphasizing the importance of strategic positioning and clinical differentiation.

Tadalafil

Tadalafil remains a top performer among PDE5 inhibitors. In 2021, its global sales exceeded USD 2 billion, with projections to surpass USD 2.5 billion by 2025[^5]. Revenue is supported by:

• Extensive patent protection in key regions until at least 2023.
• Diversified indications facilitating steady revenue streams.
• The shift toward combination therapies for ED and BPH.

Historical patent losses and the advent of generics threaten margins, but ongoing formulations for pulmonary hypertension and other conditions promise revenue diversification. Additionally, preferences for long-acting formulations support sustained market presence.

Emerging Trends Influencing Market Trajectory

1. Biosimilars and Generics

Patent expirations, notably for tadalafil, are ushering in increased generic competition, pressuring pricing and margins. The advent of biosimilars for other PAH therapies signifies industry evolution, although macitentan’s patent life remains a critical factor.

2. Personalized Medicine and Biomarkers

Advances in genetic profiling and biomarkers could refine patient selection for therapies, leading to better outcomes and potentially higher adoption rates for drugs like macitentan.

3. Digital and Telemedicine Integration

Enhanced monitoring and telemedicine services can improve treatment adherence and outcomes, indirectly influencing sales volume for chronic therapies.

4. Novel Delivery Systems

Development of sustained-release formulations or combination delivery systems could extend product lifecycle and expand indications, impacting financial trajectories positively.

Regulatory and Macroeconomic Considerations

Stringent regulatory standards for safety and efficacy influence product approval timelines and market entry. Economic pressures in healthcare systems may favor cost-effective generics, impacting branded drug revenues. Conversely, emerging markets with rising healthcare spending present growth opportunities for both compounds.

Key Market Risks

• Regulatory hurdles delaying or restricting access.
• Pricing pressures and reimbursement limitations.
• High dependence on indications susceptible to market saturation.
• Patent cliffs leading to revenue erosion.

Conclusion and Strategic Outlook

Macitentan is positioned for moderate growth, contingent on successful indication expansion and regional penetration. Its trajectory hinges on clinical outcomes, regulatory approval of new uses, and regional access.

Tadalafil continues to enjoy robust sales, supported by diversified indications and long-standing market presence. Its future growth may derive from biosimilar competition, innovation in formulations, and market expansion in emerging economies.

To maximize opportunities, industry stakeholders should focus on enhancing clinical evidence, optimizing pricing strategies, safeguarding patent exclusivity, and expanding into high-growth markets.

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Key Takeaways

• The market for macitentan is characterized by steady growth driven by PAH prevalence, regulatory approvals, and signficant clinical differentiation, with forecasts indicating a potential USD 700 million global market by 2025.
• Tadalafil’s extensive indication portfolio and entrenched market position support annual sales exceeding USD 2 billion, though patent expiries open pathways for competitive pressures and generics.
• Emerging trends such as biosimilars, personalized medicine, and innovative formulations are shaping future revenue streams for both drugs.
• Pricing and reimbursement policies significantly influence market penetration and revenue potential, especially amid increasing healthcare cost containment measures.
• Regulatory risks, patent expirations, and market saturation instigate strategic considerations for sustained financial performance.

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FAQs

1. How will the patent expiration of tadalafil impact its market share?
Patent expiration will likely lead to significant generic competition, exerting downward pressure on prices and margins, although sustained revenues from formulations and expanding indications may offset some losses.

2. What are the key differentiators for macitentan in the PAH market?
Its improved safety profile, once-daily dosing, and demonstrated efficacy distinguish macitentan from earlier endothelin receptor antagonists, strengthening its market position.

3. Are there upcoming regulatory approvals that could influence these drugs’ trajectories?
Yes, ongoing clinical trials and regulatory submissions for new indications or formulations could enhance market opportunities, particularly for macitentan in additional vascular conditions.

4. How does pricing strategy influence the long-term success of these drugs?
Competitive pricing, aligned with demonstrated clinical value, influences reimbursement success, market penetration, and revenue sustainability, especially in price-sensitive markets.

5. What role do emerging markets play in the future growth of macitentan and tadalafil?
Growing healthcare infrastructure and increased disease awareness in emerging markets offer substantial opportunities for increased adoption, provided regulatory and pricing hurdles are managed effectively.

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Sources

1. Pulmonary Arterial Hypertension (PAH) Drugs Market Overview (2022), MarketsandMarkets.
2. Global Pulmonary Arterial Hypertension Drugs Market Forecast (2022-2027), ResearchAndMarkets.
3. Global PDE5 Inhibitors Market Report (2022), Grand View Research.
4. Johnson & Johnson Annual Report (2021).
5. Eli Lilly Financial Reports (2021).