Leflunomide - Generic Drug Details

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

Leflunomide is the generic ingredient in two branded drugs marketed by Sanofi Aventis Us, Abhai Llc, Aet Pharma, Alembic Pharms Ltd, Apotex, Aurobindo Pharma, Barr, Fosun Wanbang, Heritage, Lupin Ltd, Sandoz, Teva Pharms, and Zydus Lifesciences, and is included in thirteen NDAs. Additional information is available in the individual branded drug profile pages.

There are seven drug master file entries for leflunomide. Seventeen suppliers are listed for this compound.

Summary for leflunomide

US Patents:	0
Tradenames:	2
Applicants:	13
NDAs:	13
Drug Master File Entries:	7
Finished Product Suppliers / Packagers:	17
Raw Ingredient (Bulk) Api Vendors:	108
Clinical Trials:	108
Patent Applications:	6,543
Drug Prices:	Drug price trends for leflunomide
What excipients (inactive ingredients) are in leflunomide?	leflunomide excipients list
DailyMed Link:	leflunomide at DailyMed

See drug prices for leflunomide

See drug sales revenues for leflunomide

Recent Clinical Trials for leflunomide

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

Sponsor	Phase
NYU Langone Health	PHASE2
West Virginia University	PHASE1
National Cancer Institute (NCI)	PHASE1

See all leflunomide clinical trials

Pharmacology for leflunomide

Drug Class

Antirheumatic Agent

Anatomical Therapeutic Chemical (ATC) Classes for leflunomide

L04AA	Selective immunosuppressants
L04A	IMMUNOSUPPRESSANTS
L04	IMMUNOSUPPRESSANTS
L	Antineoplastic and immunomodulating agents

L04AK	Dihydroorotate dehydrogenase (DHODH) inhibitors
L04A	IMMUNOSUPPRESSANTS
L04	IMMUNOSUPPRESSANTS
L	Antineoplastic and immunomodulating agents

US Patents and Regulatory Information for leflunomide

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Lupin Ltd	LEFLUNOMIDE	leflunomide	TABLET;ORAL	211863-001	Feb 4, 2020	AB	RX	No	No
Fosun Wanbang	LEFLUNOMIDE	leflunomide	TABLET;ORAL	077087-002	Sep 13, 2005	AB	RX	No	No
Zydus Lifesciences	LEFLUNOMIDE	leflunomide	TABLET;ORAL	212308-001	Apr 24, 2019	AB	RX	No	No
Sanofi Aventis Us	ARAVA	leflunomide	TABLET;ORAL	020905-001	Sep 10, 1998	AB	RX	Yes	No
Apotex	LEFLUNOMIDE	leflunomide	TABLET;ORAL	077090-001	Sep 13, 2005	AB	RX	No	No

Expired US Patents for leflunomide

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Sanofi Aventis Us	ARAVA	leflunomide	TABLET;ORAL	020905-003	Sep 10, 1998
Sanofi Aventis Us	ARAVA	leflunomide	TABLET;ORAL	020905-001	Sep 10, 1998
Sanofi Aventis Us	ARAVA	leflunomide	TABLET;ORAL	020905-003	Sep 10, 1998
Sanofi Aventis Us	ARAVA	leflunomide	TABLET;ORAL	020905-003	Sep 10, 1998
Sanofi Aventis Us	ARAVA	leflunomide	TABLET;ORAL	020905-002	Sep 10, 1998

EU/EMA Drug Approvals for leflunomide

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Zentiva k.s.	Leflunomide Zentiva (previously Leflunomide Winthrop)	leflunomide	EMEA/H/C/001129Leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (DMARD);active psoriatic arthritis.Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.Moreover, switching from leflunomide to another DMARD without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.	Authorised	no	no	no	2010-01-08
Ratiopharm GmbH	Leflunomide ratiopharm	leflunomide	EMEA/H/C/002035Leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (DMARD);active psoriatic arthritis.Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.Moreover, switching from leflunomide to another DMARD without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.	Authorised	yes	no	no	2010-11-28
medac Gesellschaft für klinische Spezialpräparate mbH	Leflunomide medac	leflunomide	EMEA/H/C/001227Leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (DMARD).Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) may result in an increased risk of serious adverse reactions, therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.Moreover, switching from leflunomide to another DMARD without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.	Authorised	yes	no	no	2010-07-27
Sanofi-aventis Deutschland GmbH	Arava	leflunomide	EMEA/H/C/000235Leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a 'disease-modifying antirheumatic drug' (DMARD);active psoriatic arthritis.Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.Moreover, switching from leflunomide to another DMARD without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.	Authorised	no	no	no	1999-09-02
Teva B.V.	Repso	leflunomide	EMEA/H/C/001222Leflunomide is indicated for the treatment of adult patients with:active rheumatoid arthritis as a ‘disease-modifying antirheumatic drug’ (DMARD);active psoriatic arthritis.Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit / risk aspects.Moreover, switching from leflunomide to another DMARD without following the washout procedure may also increase the risk of serious adverse reactions even for a long time after the switching.	Withdrawn	yes	no	no	2011-03-14

Market Dynamics and Financial Trajectory for Leflunomide

Last updated: July 27, 2025

Introduction

Leflunomide, an immunomodulatory agent marketed primarily as Arava®, has established itself as a cornerstone in managing rheumatoid arthritis (RA) and other autoimmune disorders. Since its inception, the drug has experienced steady growth driven by evolving therapeutic needs, patent protections, and expanding indications. This analysis explores the current market landscape, key drivers, competitive forces, and financial outlooks shaping the future trajectory of leflunomide.

Pharmacological Profile and Therapeutic Use

Leflunomide is an oral disease-modifying anti-rheumatic drug (DMARD) that inhibits pyrimidine synthesis, thus dampening lymphocyte proliferation. Approved by the U.S. Food and Drug Administration (FDA) in 1998, its primary indication has been moderate to severe RA, often considered alongside methotrexate, sulfasalazine, and biologics. Recent off-label uses include psoriatic arthritis and ankylosing spondylitis, broadening its potential market.

Market Dynamics

1. Market Size and Growth Trends

The global RA therapeutics market, valued at approximately $22 billion in 2022, is projected to reach around $35 billion by 2030, growing at a CAGR of 6-7% (2023-2030). Leflunomide’s share within this segment remains significant but faces intensifying competition from biologics and targeted synthetic DMARDs.

The demand for oral, cost-effective therapies continues to favor leflunomide, especially in regions with healthcare cost constraints. Its established efficacy and familiar safety profile sustain its position, particularly in North America and Europe, where the biologics market is saturated but often limited by reimbursement challenges.

2. Patent Lifecycle and Generic Entry

Leflunomide's original patent protection, held by Sanofi-Aventis, expired in the early 2010s in major markets, leading to parity generics entering the market. This has resulted in a sharp decline in branded drug revenue but increased accessibility and affordability.

Despite patent expiry, Sanofi and other manufacturers retain market share through strategic patents on formulations, dosing regimens, and combinations, often delaying full generic penetration in certain regions.

3. Competitive Landscape

The market faces competition from:

• Biologic agents such as adalimumab, etanercept, and infliximab, which exhibit higher efficacy but at increased costs.
• Targeted synthetic DMARDs like tofacitinib and baricitinib, offering oral administration with comparable efficacy.
• Emerging biosimilars that further reduce costs and enhance accessibility.

Leflunomide's future competitiveness hinges upon its positioning relative to these alternatives, with factors like safety profile, cost-effectiveness, and clinician familiarity influencing prescribing trends.

4. Regulatory and Reimbursement Environment

Regulatory approval extends primarily within developed markets, with some emerging economies adopting generic versions. Reimbursement policies favor cost-effective treatments, bolstering leflunomide's usage where biologics remain financially prohibitive.

Policy shifts towards value-based care and biosimilars could either marginalize leflunomide further or reinforce its role as a first-line adjunct therapy, depending on clinical protocols.

Financial Trajectory

1. Revenue Projections

Following patent expiration, branded sales declined by over 50% within five years in key markets. However, global demand persists, especially in underserved regions.

Forecasts suggest:

• A moderate recovery in revenue driven by new formulations (e.g., fixed-dose combinations) and expanded indications such as psoriatic arthritis.
• Steady decline in mature markets due to generic competition, with revenues stabilizing around $300-500 million annually globally by 2025.

2. Price Trends and Cost Dynamics

The introduction of generics significantly reduced unit prices. Nonetheless, manufacturing efficiencies and economies of scale have somewhat offset revenue loss.

Investments in lifecycle management, including patent extensions via method-of-use patents or formulation innovations, could buttress market share.

3. Investment Outlook and R&D

Limited pipeline development for leflunomide suggests the focus remains on optimizing its current formulations rather than novel indications. Future R&D investments are potentially concentrated on combination therapies or biomarker-driven personalized medicine, which could rejuvenate its market appeal.

Strategic Opportunities and Challenges

• Opportunities: Expansion into emerging markets, combination therapy patents, and repositioning in new autoimmune indications.
• Challenges: Rising competition from biologics and biosimilars, reimbursement pressures, and the need for differentiation beyond cost.

Conclusion

Leflunomide's market dynamics are characterized by a declining branded segment offset by broader access and stable demand in less saturated regions. Financially, its trajectory faces headwinds from generic competition, yet opportunities exist through strategic innovation and market expansion. Stakeholders must balance cost strategies with ongoing clinical demands and regulatory evolution to preserve its relevance.

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Key Takeaways

• The leflunomide market is mature, with revenues declining post-patent expiration but still sustaining a significant share in global RA treatment.
• Competition from biologics and biosimilars intensifies, challenging leflunomide’s traditional position.
• Cost-effective oral DMARDs continue to favor leflunomide’s relevance, especially in emerging markets.
• Lifecycle management strategies, such as formulation improvements and expanded indications, are key to maintaining financial viability.
• Market entrants and regulatory shifts will influence future demand, necessitating adaptive commercialization tactics.

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FAQs

1. How has patent expiry affected leflunomide’s market share?
Patent expiration led to an influx of low-cost generics, significantly reducing branded revenues. However, ongoing clinical use and regional accessibility maintain its market presence, especially where biologics are less affordable.

2. What are the main competitors to leflunomide in RA management?
Biologics like adalimumab and etanercept, and targeted synthetic DMARDs such as tofacitinib, represent primary competition, offering higher efficacy but at greater cost.

3. Can leflunomide be repositioned for new indications?
Potential exists for expanding into psoriatic arthritis and ankylosing spondylitis, contingent on clinical trial data and regulatory approval, which could enhance its financial outlook.

4. What role do biosimilars play in the future of leflunomide?
While biosimilars target biologic drugs, they do not directly threaten leflunomide but impact the broader RA treatment landscape, emphasizing the importance of cost and convenience.

5. What strategies can pharmaceutical companies employ to sustain leflunomide’s market?
Innovative formulation, combination therapies, lifecycle patent extensions, and targeting emerging markets with tailored pricing can prolong its commercial viability.

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Sources:

1. "Rheumatoid arthritis market analysis." MarketWatch, 2023.
2. "Leflunomide (Arava) Overview." FDA, 2022.
3. "Global autoimmune therapeutics market forecast." GlobalData, 2023.
4. "Impact of biosimilars on biologic markets." IMS Health, 2022.
5. "Patent expiration and generic entry in the pharmaceutical industry." WHO, 2021.