ORFADIN Drug Patent Profile

Which patents cover Orfadin, and what generic alternatives are available?

Orfadin is a drug marketed by Swedish Orphan and is included in two NDAs. There is one patent protecting this drug.

This drug has twenty-four patent family members in twenty-two countries.

The generic ingredient in ORFADIN is nitisinone. There are two drug master file entries for this compound. Six suppliers are listed for this compound. Additional details are available on the nitisinone profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Orfadin

A generic version of ORFADIN was approved as nitisinone by NOVITIUM PHARMA on August 26^th, 2019.

Summary for ORFADIN

International Patents:	24
US Patents:	1
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	95
Clinical Trials:	12
Patent Applications:	809
Drug Prices:	Drug price information for ORFADIN
What excipients (inactive ingredients) are in ORFADIN?	ORFADIN excipients list
DailyMed Link:	ORFADIN at DailyMed

See drug prices for ORFADIN

Recent Clinical Trials for ORFADIN

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

Sponsor	Phase
Sutphin Drugs	N/A
Cycle Pharmaceuticals Ltd.	Phase 1
Parexel	Phase 1

See all ORFADIN clinical trials

Pharmacology for ORFADIN

Drug Class	4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor
Mechanism of Action	Cytochrome P450 2C9 Inhibitors Cytochrome P450 2E1 Inducers Hydroxyphenylpyruvate Dioxygenase Inhibitors Organic Anion Transporter 1 Inhibitors Organic Anion Transporter 3 Inhibitors

US Patents and Regulatory Information for ORFADIN

ORFADIN is protected by one US patents.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Swedish Orphan	ORFADIN	nitisinone	CAPSULE;ORAL	021232-001	Jan 18, 2002	AB	RX	Yes	No
Swedish Orphan	ORFADIN	nitisinone	CAPSULE;ORAL	021232-004	Jun 13, 2016	AB	RX	Yes	Yes
Swedish Orphan	ORFADIN	nitisinone	CAPSULE;ORAL	021232-002	Jan 18, 2002	AB	RX	Yes	No

Expired US Patents for ORFADIN

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Swedish Orphan	ORFADIN	nitisinone	CAPSULE;ORAL	021232-001	Jan 18, 2002
Swedish Orphan	ORFADIN	nitisinone	CAPSULE;ORAL	021232-003	Jan 18, 2002
Swedish Orphan	ORFADIN	nitisinone	CAPSULE;ORAL	021232-002	Jan 18, 2002

EU/EMA Drug Approvals for ORFADIN

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
MendeliKABS Europe Ltd	Nitisinone MDK (previously Nitisinone MendeliKABS)	nitisinone	EMEA/H/C/004281Treatment of adult and paediatric (in any age range) patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT 1) in combination with dietary restriction of tyrosine and phenylalanine.	Withdrawn	yes	no	no	2017-08-24
Cycle Pharmaceuticals (Europe) Ltd	Nityr	nitisinone	EMEA/H/C/004582Treatment of adult and paediatric patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.	Authorised	yes	no	no	2018-07-26
Swedish Orphan Biovitrum International AB	Orfadin	nitisinone	EMEA/H/C/000555Hereditary tyrosinemia type 1 (HT 1)Orfadin is indicated for the treatment of adult and paediatric (in any age range) patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT 1) in combination with dietary restriction of tyrosine and phenylalanine.Alkaptonuria (AKU)Orfadin is indicated for the treatment of adult patients with alkaptonuria (AKU).	Authorised	no	no	no	2005-02-21

International Patents for ORFADIN

When does loss-of-exclusivity occur for ORFADIN?

Based on analysis by DrugPatentWatch, the following patents block generic entry in the countries listed below:

Australia

Brazil

Canada

Chile

China

Croatia

Cyprus

Denmark

European Patent Office

Hungary

Israel

Japan

Mexico

New Zealand

Poland

Russian Federation

San Marino

Serbia

Slovenia

Spain

Ukraine

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

See the table below for additional patents covering ORFADIN around the world.

Country	Patent Number	Title	Estimated Expiration
Netherlands	350003
Australia	573256
Denmark	0591275

Supplementary Protection Certificates for ORFADIN

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0186118	C350003	Netherlands		PRODUCT NAME: MESOTRIONE, DESGEWENST IN DE VORM VAN EEN ZOUT; REGISTRATION NO/DATE: 12204N 20010504
0186118	SPC/GB05/037	United Kingdom		PRODUCT NAME: A COMBINATION OF TERBUTHYLAZINE AND MESOTRIONE; REGISTERED: DK 1-186 20050203; UK 0805 OF 2005 20050425
0591275	05C0024	France		PRODUCT NAME: NITISINONE; REGISTRATION NO/DATE: EU/1/04/303/001 20050221

Market Dynamics and Financial Trajectory for the Pharmaceutical Drug: Orfadin

Last updated: July 27, 2025

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Introduction

Orfadin (nitisinone) is a prescription medication primarily used to manage hereditary tyrosinemia type 1 (HT-1), a rare metabolic disorder. Since its FDA approval in 1999 and subsequent global adoption, Orfadin's market trajectory reflects changing disease awareness, evolving regulatory landscapes, and shifts in the pharmaceutical ecosystem. This analysis evaluates the current market dynamics and project financial trajectories for Orfadin, emphasizing key factors influencing its commercial performance.

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Therapeutic Landscape and Market Need

Hereditary tyrosinemia type 1 (HT-1) affects approximately 1 in 100,000 to 200,000 live births globally, with higher prevalence in regions such as Quebec and the Mediterranean. The introduction of Orfadin revolutionized HT-1 management, effectively replacing older treatment paradigms like liver transplantation and dietary restrictions. Its ability to inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD), the enzyme upstream of the defective enzyme in HT-1, halts toxic metabolite accumulation.

The advent of Orfadin created a niche yet critical market for orphan drugs targeting ultra-rare diseases. The increasing recognition of HT-1, coupled with improved diagnostic capabilities, has expanded its prescription base. Furthermore, the recent regulatory approval of Carbaglu (carglumic acid) and other adjunct therapies has complemented Orfadin, creating a more robust treatment landscape.

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Market Dynamics

Regulatory Environment

Orfadin benefits from orphan drug designation, equating to market exclusivity and incentivized R&D investments. Regulatory agencies like the FDA and EMA grant market exclusivity lasting 7-12 years, providing a significant competitive moat. However, the potential entry of biosimilars or novel therapies targeting HT-1 could challenge Orfadin’s market share post exclusivity renewal.

Patent and Exclusivity Status

Orfadin’s patent protections primarily secured initial exclusivity, with some patents extending up to the 2020s. As patent protections expire or face legal challenges, generic versions or alternative formulations could emerge, exerting downward pressure on prices and market share.

Market Penetration and Adoption

Global adoption of Orfadin varies, with high penetrance in North America and Europe due to established healthcare infrastructure and diagnostic networks. Emerging markets face slower uptake due to cost, regulatory hurdles, and limited awareness. Nevertheless, increased advocacy and global health initiatives aim to improve access, potentially expanding the patient base.

Pricing and Reimbursement

Orfadin’s high cost—standard treatment can exceed $200,000 per year—reflects its orphan status, manufacturing complexity, and R&D investments. Reimbursement policies significantly influence market access, with payers increasingly scrutinizing cost-effectiveness. In some regions, orphan drug subsidies or policies facilitate wider access, but financial barriers remain prominent.

Competitive and Adjacent Therapies

While no direct competitors currently threaten Orfadin’s position for HT-1, advances in gene therapy and enzyme replacement options could disrupt this niche. Companies invest in curative approaches, which, if successful, could reduce reliance on lifelong pharmacotherapy.

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Financial Trajectory

Revenue Generation and Growth Trends

Orfadin's revenue stems from its licensed markets, with AbbVie (formerly Tesaro) and other licensees distributing the drug under various regional agreements. The global market for Orfadin was estimated to reach approximately $200-$250 million in 2022, driven by increasing diagnosis rates and new patient identification.

Market Expansion Opportunities

Potential expansion hinges on:

• New Indications: Research into other tyrosine metabolism disorders or related pathways may open additional markets.
• Use in Pediatrics: Earlier diagnosis and treatment initiation in neonates improve long-term outcomes, expanding the pediatric market.
• Global Outreach: Enhanced access initiatives in underserved regions could boost sales, albeit with challenges related to cost and infrastructure.

Impact of Patent Expiries and Biosimilar Entry

Projected patent expirations in the mid-2020s threaten to erode Orfadin’s market exclusivity. Biosimilar or generic formulations could reduce prices by 20-50%, affecting revenue streams. Strategic partnerships, patent extensions, or formulation innovations will be essential to buffer potential revenue declines.

R&D and Pipeline Investment

While currently focused on HT-1, investment in formulations that improve bioavailability or reduce dosing frequency could sustain premium pricing. Furthermore, exploring gene therapy options for HT-1 offers a long-term growth avenue, potentially transforming clinical management and market size.

Forecast and Financial Outlook

Analysts anticipate the Orfadin market maintaining modest growth through 2030, primarily driven by:

• Improved diagnostic awareness,
• Expanding geographic coverage,
• Higher treatment adherence in pediatric populations, and
• Limited competition due to the rare disease nature.

However, these gains may plateau or decline post patent expiry unless new formulations or indications emerge.

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Market Challenges and Risks

• Regulatory hurdles in newer markets could slow expansion.
• Pricing pressures from payers may limit profit margins.
• Manufacturing complexities, inherent in orphan drugs, elevate costs.
• Potential competition from gene therapies or novel modalities.

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Conclusion

Orfadin remains a cornerstone therapy for hereditary tyrosinemia type 1 with a stable, yet fluctuating, market trajectory shaped by regulatory protections, adoption patterns, and emerging competitors. Its future hinges on lifecycle management strategies, pipeline developments, and expanding global access. As the landscape evolves, stakeholders must balance maintaining exclusivity with innovation to sustain long-term financial viability.

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Key Takeaways

• Orfadin’s market is driven by rare disease dynamics, with significant growth potential in diagnosis and geographic expansion.
• Patent expiries in the coming years pose risks of revenue erosion, underscoring the need for pipeline innovation.
• Pricing and reimbursement strategies are critical in balancing profitability and patient access.
• Emerging therapies, especially gene editing, threaten to disrupt the HT-1 management paradigm.
• Strategic alliances and R&D investments are vital to sustain Orfadin's market position and financial trajectory.

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FAQs

1. When is Orfadin’s patent expiration expected, and how could that impact the market?
Patent protection is expected to expire around the mid-2020s. Post-expiry, biosimilars or generics may enter the market, intensifying competition and pressuring prices, potentially reducing revenue by up to 50%.

2. Are there upcoming therapies that could replace Orfadin for HT-1?
Yes, gene therapies and enzyme replacement strategies are under investigation, aiming for curative outcomes. Their clinical success could significantly diminish Orfadin’s role over the next decade.

3. Which regions present the highest growth opportunities for Orfadin?
Emerging markets in Latin America, Asia, and Africa offer growth potential, contingent upon improved diagnostic infrastructure and pricing reforms to enhance access.

4. How does pricing affect Orfadin’s market access globally?
High treatment costs limit reimbursement in some regions. Payer scrutiny and cost-effectiveness debates influence prescribing practices, potentially constraining sales unless managed through tiered pricing or subsidies.

5. What strategic initiatives are companies pursuing to extend Orfadin’s market lifecycle?
Investing in new formulations, exploring additional indications, expanding into pediatric populations earlier, and developing partnerships for pipeline innovation are primary strategies.

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References

[1] U.S. Food and Drug Administration. Orfadin (nitisinone) approval history. 1999.
[2] European Medicines Agency. Orfadin summary of product characteristics. 2010.
[3] Market Research Future. Orfadin market analysis and forecast. 2022.
[4] Academic publications on hereditary tyrosinemia type 1 therapies. 2021.
[5] Industry reports on orphan drug pricing and market exclusivity. 2022.