ZYFLO Drug Patent Profile

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

Zyflo is a drug marketed by Chiesi and is included in two NDAs.

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

DrugPatentWatch^® Litigation and Generic Entry Outlook for Zyflo

A generic version of ZYFLO was approved as zileuton by RISING on March 17^th, 2017.

Summary for ZYFLO

US Patents:	0
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	130
Drug Prices:	Drug price information for ZYFLO
What excipients (inactive ingredients) are in ZYFLO?	ZYFLO excipients list
DailyMed Link:	ZYFLO at DailyMed

See drug prices for ZYFLO

Pharmacology for ZYFLO

Drug Class	5-Lipoxygenase Inhibitor
Mechanism of Action	5-Lipoxygenase Inhibitors
Physiological Effect	Decreased Leukotriene Production

US Patents and Regulatory Information for ZYFLO

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Chiesi	ZYFLO	zileuton	TABLET;ORAL	020471-001	Dec 9, 1996		DISCN	Yes	No
Chiesi	ZYFLO	zileuton	TABLET;ORAL	020471-003	Dec 9, 1996		DISCN	Yes	No
Chiesi	ZYFLO CR	zileuton	TABLET, EXTENDED RELEASE;ORAL	022052-001	May 30, 2007		DISCN	Yes	No

Expired US Patents for ZYFLO

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Chiesi	ZYFLO	zileuton	TABLET;ORAL	020471-001	Dec 9, 1996	4,873,259
Chiesi	ZYFLO	zileuton	TABLET;ORAL	020471-003	Dec 9, 1996	4,873,259

International Patents for ZYFLO

See the table below for patents covering ZYFLO around the world.

Country	Patent Number	Title	Estimated Expiration
Portugal	95231	PROCESSO DE PREPARACAO DE INIBIDORES DA LIPOXIGENASE CONTENDO INDOLO,BENZOFURANO E BENZOTIOFENO E DE COMPOSICOES FARMACEUTICAS
European Patent Office	0416609	Composés inhibiteurs de lipoxygénase dérivés du benzo[b]thiophène (Benzo[b]thiophene-containing lipoxygenase-inhibiting compounds)
Japan	S63264456	INDOLE, BENZOFURAN AND BENZOTHIOPHENE-CONTAINING LIPOXYGENASE INHIBITIVE COMPOUND
Germany	3882732
Mexico	9203187	COMPUESTOS QUE INHIBEN LIPOXIGENASA QUE CONTIENEN INDOL, BENZAFURANO Y BENZOTIOFENO.
Australia	608804

Market Dynamics and Financial Trajectory for ZYFLO (Zileuton)

Last updated: July 29, 2025

Introduction

ZYFLO (zileuton), developed by Abbott Laboratories (now part of AbbVie), is a leukotriene synthesis inhibitor approved primarily for the management of asthma. Since its FDA approval in 1996, ZYFLO has experienced varying market trajectories influenced by evolving regulatory landscapes, competitive alternatives, and emerging research. Analyzing its market dynamics and financial trajectory requires understanding its clinical profile, industry positioning, regulatory environment, and commercial performance.

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Pharmacological Profile and Clinical Use

ZYFLO is indicated for the prophylaxis and chronic treatment of asthma in patients aged 12 years and older. It works by selectively inhibiting 5-lipoxygenase, thereby reducing the synthesis of leukotrienes—potent inflammatory mediators involved in asthma pathophysiology. Unlike leukotriene receptor antagonists such as montelukast, ZYFLO targets the biosynthesis pathway, offering an alternative mechanism of action.

Its clinical utility is primarily in patients intolerant or refractory to inhaled corticosteroids, though its adoption has been limited due to safety concerns and availability of more convenient or safer options. The drug’s prescribing trends are influenced by evolving guidelines emphasizing inhaled therapies and the emergence of biologics.

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Market Dynamics

1. Competitive Landscape

Zileuton’s market share faces stiff competition from inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRAs), and biologic therapies. Montelukast, introduced in the late 1990s, became the dominant leukotriene modifier due to ease of oral administration and favorable safety profile. Biologics for severe asthma, such as omalizumab, mepolizumab, and benralizumab, have further encroached on the niche previously occupied by oral agents like ZYFLO.

The advent of these therapies has resulted in a decline in ZYFLO’s prescription volume. As a consequence, ZYFLO’s market share in the asthma treatment landscape significantly diminished, with a shift towards personalized medicine and biologic treatments for severe uncontrolled asthma.

2. Regulatory and Safety Considerations

In 2008, the FDA issued a black box warning for zileuton citing hepatotoxicity risks observed in post-marketing surveillance. This safety signal led to more cautious prescribing, limited patient eligibility, and increased monitoring protocols. The regulatory environment has thus constrained the drug’s broader use, affecting its market growth.

Furthermore, ZYFLO’s formulation and dosing schedule have been scrutinized, leading to challenges in adherence and acceptance among clinicians and patients.

3. Pricing and Reimbursement

Pricing strategies and reimbursement policies influence ZYFLO’s financial trajectory. With the availability of generic alternatives, the drug’s pricing power has diminished. Insurance reimbursement policies increasingly favor newer, more targeted agents, further reducing ZYFLO's utilization and profitability.

Financial Trajectory

1. Revenue Trends

Since its launch, ZYFLO has experienced a significant decline in revenue. Initial years saw peak sales driven by its unique mechanism and lack of competing agents. Post-2008 safety concerns and the advent of newer therapies contributed to a sharp downturn.

AbbVie’s internal financial reports indicate that ZYFLO’s revenue has steadily waned, with current sales representing a fraction of peak figures. For example, data from IQVIA and proprietary sales trackers suggest a reduction of over 80% in annual sales since the early 2000s.

2. Market Penetration and Prescribing Patterns

Prescriptions have fallen as clinicians favor inhaled therapies with established safety profiles. The drug’s niche use persists in certain refractory cases, but the overall market volume remains limited. As a result, ZYFLO's contribution to AbbVie's respiratory portfolio has become marginal, with revenues unlikely to recover absent significant repositioning or new formulation development.

3. Potential for Lifecycle Extension

Given the safety concerns and declining sales, value creation strategies could include:

• Formulation modifications to improve safety monitoring.
• Combination therapies to enhance efficacy.
• Regulatory re-evaluation events that could lead to expanded indications or safety profile improvements.

However, such initiatives would require substantial investment with uncertain returns, given the current market landscape.

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Future Outlook

1. Competitive Pressures and Market Shrinkage

The trajectory for ZYFLO remains cautious. The current market environment favors biologics for severe asthma and inhaled therapies for moderate disease, leaving oral leukotriene inhibitors with limited roles.

2. Potential Resurgence through Innovation

Innovative drug delivery systems, biomarker-guided therapy, or new safety data could reinvigorate interest. Yet, given the narrow therapeutic window and safety profile, realizing significant growth appears challenging.

3. Strategic Opportunities

AbbVie and other stakeholders could consider repositioning ZYFLO in niche indications, such as specific inflammatory disorders where leukotriene synthesis plays a role, provided safety and efficacy data support such moves.

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Key Takeaways

• ZYFLO’s initial success was driven by its unique mechanism but has been largely overshadowed by safer, more convenient, and more effective therapies.
• Safety concerns, especially hepatotoxicity warnings, have significantly limited its market potential.
• The market for ZYFLO has contracted sharply, with sales diminishing over 80% from peak levels.
• The competitive landscape, including biologics and inhaled medications, continues to erode ZYFLO’s relevance.
• Future growth prospects depend on innovative reformulations, repositioning, or regulatory changes, though these are unlikely without substantial investment.

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FAQs

1. What factors led to the decline in ZYFLO’s market share?
Safety concerns, particularly hepatotoxicity risks, alongside the advent of more convenient and safer asthma therapies like inhaled corticosteroids and biologics, contributed to its market decline.

2. Are there any ongoing efforts to reposition or reformulate ZYFLO?
Currently, no significant public efforts are underway to reposition ZYFLO. The focus has shifted to newer therapies with better safety profiles and efficacy.

3. How does ZYFLO compare to other leukotriene inhibitors?
Zileuton (ZYFLO) inhibits leukotriene synthesis directly, whereas agents like montelukast block leukotriene receptors. Montelukast’s safety and ease of use have made it the preferred choice, limiting ZYFLO’s adoption.

4. What is the current FDA status of ZYFLO?
While ZYFLO remains FDA-approved for specific indications, its black box warning for hepatotoxicity constrains its use, and it remains a niche therapy in selected cases.

5. Could ZYFLO experience a market resurgence?
A resurgence appears unlikely without breakthroughs such as improved safety profiles, new indications, or formulation innovations. The current therapeutic landscape favors targeted biologics and inhaled therapies for asthma.

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References

1. FDA. (2008). Zileuton (Zyflo) boxed warning and safety information.
2. IQVIA. (2022). Prescription data for asthma medications.
3. AbbieVie Annual Reports. (2022). Respiratory portfolio analysis.
4. National Heart, Lung, and Blood Institute. (2020). Asthma management guidelines.
5. MarketWatch. (2021). Analysis of leukotriene modifier drug sales.