KUVAN Drug Patent Profile

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

Kuvan is a drug marketed by Biomarin Pharm and is included in two NDAs. There are ten patents protecting this drug and three Paragraph IV challenges.

This drug has one hundred and seventeen patent family members in twenty-six countries.

The generic ingredient in KUVAN is sapropterin dihydrochloride. There are three drug master file entries for this compound. Nine suppliers are listed for this compound. Additional details are available on the sapropterin dihydrochloride profile page.

DrugPatentWatch^® Litigation and Generic Entry Outlook for Kuvan

A generic version of KUVAN was approved as sapropterin dihydrochloride by PH HEALTH on May 10^th, 2019.

Summary for KUVAN

International Patents:	117
US Patents:	10
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	65
Patent Applications:	355
Drug Prices:	Drug price information for KUVAN
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for KUVAN
What excipients (inactive ingredients) are in KUVAN?	KUVAN excipients list
DailyMed Link:	KUVAN at DailyMed

See drug prices for KUVAN

Pharmacology for KUVAN

Drug Class	Phenylalanine Hydroxylase Activator
Mechanism of Action	Breast Cancer Resistance Protein Inhibitors P-Glycoprotein Inhibitors Phenylalanine Hydroxylase Activators

Paragraph IV (Patent) Challenges for KUVAN

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
KUVAN	Powder for Oral Solution	sapropterin dihydrochloride	500 mg per packet	205065	1	2017-02-23
KUVAN	Powder for Oral Solution	sapropterin dihydrochloride	100 mg per packet	205065	1	2015-11-09
KUVAN	Tablets	sapropterin dihydrochloride	100 mg	022181	1	2014-06-05

US Patents and Regulatory Information for KUVAN

KUVAN is protected by six US patents.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-001	Dec 19, 2013	AB	RX	Yes	Yes	8,067,416*PED				Y
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	TABLET;ORAL	022181-001	Dec 13, 2007	AB	RX	Yes	Yes	8,067,416*PED				Y
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-002	Oct 27, 2015	AB	RX	Yes	No	7,612,073*PED				Y
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-001	Dec 19, 2013	AB	RX	Yes	Yes	7,566,714*PED				Y
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-002	Oct 27, 2015	AB	RX	Yes	No	9,433,624*PED				Y
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	TABLET;ORAL	022181-001	Dec 13, 2007	AB	RX	Yes	Yes	RE43797*PED				Y

Expired US Patents for KUVAN

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	TABLET;ORAL	022181-001	Dec 13, 2007	8,067,416*PED
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-001	Dec 19, 2013	7,566,714*PED
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-002	Oct 27, 2015	8,067,416*PED
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-002	Oct 27, 2015	RE43797*PED
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-001	Dec 19, 2013	RE43797*PED
Biomarin Pharm	KUVAN	sapropterin dihydrochloride	POWDER;ORAL	205065-002	Oct 27, 2015	7,566,714*PED

International Patents for KUVAN

When does loss-of-exclusivity occur for KUVAN?

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

Japan

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 KUVAN around the world.

Country	Patent Number	Title	Estimated Expiration
Croatia	P20210239
Portugal	3461503
Slovenia	2545939
Brazil	PI0821970
Slovenia	3138566
Mexico	2007005039	FORMULACION DE TABLETA ESTABLE. (STABLE TABLET FORMULATION OF TETRAHYDROBIOPTERIN.)

Market Dynamics and Financial Trajectory for KUVAN

Last updated: December 26, 2025

Executive Summary

KUVAN (sapropterin dihydrochloride) is a pharmaceutical agent developed by BioMarin Pharmaceutical, approved primarily for the treatment of phenylketonuria (PKU), a rare inherited metabolic disorder. As a pioneering therapy within Orphan Drug status, KUVAN's market trajectory has been shaped by evolving industry dynamics, regulatory landscapes, and diagnosis rates of PKU. This report delves into the current market environment, competitive positioning, revenue projections, and strategic factors influencing KUVAN’s financial outlook.

---

What is KUVAN and How Does It Function?

Attribute	Details
Generic Name	Sapropterin dihydrochloride
Brand Name	KUVAN
Approved Indications	Phenylketonuria (PKU)
Manufacturer	BioMarin Pharmaceutical Inc.
Formulation	Oral tablets, powder for oral solution
Mechanism of Action	Enhances residual phenylalanine hydroxylase enzyme activity, reducing phenylalanine levels

Note: KUVAN is classified as an orphan drug, benefiting from incentives like market exclusivity and tax credits under US and international policies.

---

How Have Market Dynamics Shaped KUVAN’s Trajectory?

1. Regulatory and Policy Environment

Aspect	Impact	Details
Orphan Drug Designation	Market exclusivity, financial incentives	US (2012), EU (2014); lasts 7-10 years
Pricing and Reimbursement	High pricing, variable coverage	US (average wholesale price ~$677,000/year), reimbursement challenges in some regions
International Approvals	Growing global access	Approved in Japan (2015), Australia, Canada, and ongoing submissions elsewhere

2. Diagnosis and Patient Population

Disease Prevalence	Data	Implication
US PKU prevalence	1 in 10,000 to 15,000 live births	Estimated 25,000–30,000 patients in US
Global estimates	Similar or higher in some European and Asian countries	Potential for market expansion

Market penetration is limited by diagnosis rates, especially in underserved regions, but increasing newborn screening has bolstered early detection.

3. Competitive Landscape

Competitors	Status	Market Position
Dietary management (phenylalanine-restricted diet)	Standard care, non-pharmacologic	Complementary to KUVAN; limits growth competition
Pegvaliase (Palynziq)	Approved in 2018 by FDA for adult PKU; enzyme substitution	Direct competitor in the pharmacologic domain, expanding treatment options
Other emerging therapies	Gene therapy trials and enzyme replacement treatments	Future potential challenges or collaboration opportunities

4. Market Challenges and Opportunities

Challenges	Opportunities
Limited patient population	Focus on rare disease, leveraging orphan drug incentives
High treatment costs	Value-based pricing discussions
Variability in insurance coverage	Policy advocacy to improve reimbursement
Lack of universal worldwide approval	Regulatory approvals in emerging markets

---

What Is KUVAN’s Financial Trajectory?

Revenue Growth and Market Share

Year	Estimated Global Sales (USD)	Key Drivers	Notes
2013	$67 million	First approved year, initial uptake	U.S. market focus
2018	$300 million	Expanded approvals, increased diagnosis awareness	Expansion into European markets; introduction of syringes/formulation diversification
2022	~$575 million	New markets, increased insurance coverage	Launch in Japan and Canada, expanded indication in EU

Table 1: KUVAN Revenue Estimates (Source: BioMarin 10-K filings[1], analyst reports[2])

Fiscal Year	US Sales	International Sales	Total Revenue	Growth Rate	Notes
2013	$50M	$17M	$67M	N/A	Launch period
2018	$210M	$90M	$300M	20% CAGR	Market expansion, reimbursement
2022	$375M	$200M	$575M	18.5% CAGR	Global adoption, new formulations

Cost and Profitability

Aspect	Data	Impact
R&D Expenses	~$75 million in 2022	Support ongoing research and pipeline development
Gross Margin	Approximately 78-82% in recent years	Favorable profitability metric
Operating Expenses	~$150 million (2022), driven by sales, marketing, R&D	Investment in market expansion and clinical trials

Forecasts and Projections

Projection Year	Expected Revenue (USD)	Key Assumptions	Source
2025	$700–$800 million	Increased global approvals, insurance coverage, and diagnosis rates	Analyst consensus
2030	$1.2–$1.5 billion	Broader access, potential label expansion, possible gene therapy competition	Industry reports[3]

---

How Do Patent and Exclusivity Policies Influence KUVAN’s Market?

Aspect	Implication	Duration/Details
Market Exclusivity	Extended competitive advantage in US and EU	7–10 years after approval
Patent Life	Protects manufacturing and molecular composition	Filed until ~2030; subject to legal challenges
Biosimilar/Generic Entry	Likely limited due to orphan status and patent protections	Reduced risk, conservative entry estimates

Key Policy Considerations

• US FDA: Data exclusivity until 2022, with patent protections until at least 2030.
• EU: Similar market exclusivity, plus national/regional patent laws.
• Global landscape: Variability; emerging markets may face delayed approvals.

---

How Do Competitive Trends and Innovation Affect KUVAN’s Future?

Trend	Impact on KUVAN	Strategic Response
Introduction of enzyme therapies (e.g., Pegvaliase)	Direct competition, especially in adult populations	Diversify indications, improve access, and patient adherence strategies
Gene therapy developments	Long-term potential to replace pharmacotherapy	Collaboration or investment in gene therapy pipelines
Improved diagnostics	Larger patient base; earlier intervention	Expand global newborn screening programs

---

Comparison Summary: KUVAN vs. Competitors

Aspect	KUVAN	Pegvaliase	Gene Therapy Approaches
Approval Year	2014	2018	Under clinical development
Treatment Type	BH4 cofactor supplementation	Enzyme substitution	Gene editing/replacement
Market Size	~$575 million (2022)	Emerging (>$180M initial)	Future potential
Cost	~$677,000/year	~$200,000/year (initial)	TBD

---

Critical Success Factors for KUVAN

• Market Expansion: Improve global awareness and access, especially in Asia and emerging regions.
• Reimbursement Optimization: Collaborate with insurers for better coverage, especially where high costs pose barriers.
• Label Expansion: Investigate additional PKU indications, such as late-onset PKU, or other inborn errors.
• Pipeline Development: Invest in next-generation therapies, including gene therapy, to sustain long-term growth.
• Patient Engagement: Enhance adherence strategies through improved formulations and education.

---

Key Takeaways

• KUVAN’s market success hinges on ongoing diagnosis expansion, reimbursement negotiations, and global regulatory approvals.
• Despite competition from enzyme substitution therapies, KUVAN maintains a dominant position due to its established safety profile and early-mover advantage within orphan drug incentives.
• Revenue projections suggest continued growth towards $700–$800 million by 2025, driven by market expansion and indication broadening.
• Patent protection and regulatory exclusivities provide critical exclusivity windows until at least 2030, reducing immediate biosimilar threat.
• Emerging therapies, particularly gene therapy, present potential future disruptors but will require several years for commercial viability.

---

FAQs

Q1. How does KUVAN’s pricing impact its market adoption?
A1. KUVAN’s high cost (~$677,000/year) presents reimbursement challenges, particularly outside the US. Market acceptance is strengthened by strong evidence of efficacy and favorable reimbursement negotiations, but affordability remains a barrier in certain regions, affecting access and growth.

Q2. What are the primary regulatory hurdles for KUVAN in international markets?
A2. Approval variability driven by differing national policies for orphan drugs, local safety standards, and the capacity to conduct comprehensive clinical trials. Japan, Canada, and Australia have approved KUVAN, but ongoing efforts focus on broader access.

Q3. How does KUVAN compare with other treatments for PKU?
A3. KUVAN offers a targeted approach by augmenting residual enzyme activity, suitable for specific mutation types. Pegvaliase and future gene therapies may provide alternatives, especially for patients non-responsive to KUVAN.

Q4. When might biosimilar versions threaten KUVAN’s market share?
A4. Likely post-2030 when patents and market exclusivities expire, but current protections and small patient population limit immediate biosimilar entry.

Q5. What is the outlook for KUVAN’s pipeline and future indications?
A5. Current focus on label expansion within PKU is promising. Long-term prospects include exploring therapy for related metabolic disorders and possible combination strategies with emerging gene therapies.

---

Sources

[1] BioMarin 10-K filings, 2013-2022.
[2] Industry Analyst Reports, 2022-2023.
[3] Market Intelligence Reports on Rare Disease Therapeutics, 2022.

Disclaimer: This analysis reflects publicly available information as of 2023 and market conditions may evolve.