CLINICAL TRIALS PROFILE FOR ZILEUTON

All Clinical Trials for zileuton

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00056004 ↗	Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia	Completed	National Cancer Institute (NCI)	Phase 2	2003-06-01	RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of zileuton may be an effective way to prevent lung cancer in patients who have bronchial dysplasia. PURPOSE: Randomized phase II trial to study the effectiveness of zileuton in preventing lung cancer in patients who have bronchial dysplasia.
NCT00056004 ↗	Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia	Completed	Barbara Ann Karmanos Cancer Institute	Phase 2	2003-06-01	RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of zileuton may be an effective way to prevent lung cancer in patients who have bronchial dysplasia. PURPOSE: Randomized phase II trial to study the effectiveness of zileuton in preventing lung cancer in patients who have bronchial dysplasia.
NCT00070486 ↗	Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer	Completed	National Cancer Institute (NCI)	Phase 2	2003-12-01	RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib and zileuton may stop the growth of tumor cells by stopping blood flow to the tumor and may block the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib and/or zileuton may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combining celecoxib and/or zileuton with carboplatin and gemcitabine in treating patients who have advanced non-small cell lung cancer.
NCT00070486 ↗	Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer	Completed	Alliance for Clinical Trials in Oncology	Phase 2	2003-12-01	RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib and zileuton may stop the growth of tumor cells by stopping blood flow to the tumor and may block the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib and/or zileuton may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combining celecoxib and/or zileuton with carboplatin and gemcitabine in treating patients who have advanced non-small cell lung cancer.
NCT00098358 ↗	Study of Oral Zileuton in the Treatment of Moderate to Severe Facial Acne Vulgaris	Unknown status	Critical Therapeutics	Phase 2	2004-11-01	Tissue inflammation is a major component of the acne disease process. Leukotriene B4 (LTB4) is thought to be a major player in the development of tissue inflammation. Synthesis of LTB4 is controlled by the enzyme 5-lipoxygenase. Zileuton blocks the activity of 5-lipoxygenase. This study will test the safety and efficacy of zileuton in the treatment of facial acne.
NCT00262405 ↗	Zileuton for the Treatment of Idiopathic Pulmonary Fibrosis	Completed	National Institutes of Health (NIH)	Phase 2	2001-01-01	Open label trial of zileuton compared to azathioprine/prednisone for patients with idiopathic pulmonary fibrosis. Study subjects will undergo a detailed clinical, radiographic, and physiologic assessment at baseline. Subjects will be monitored off treatment for three months for changes in symptoms and physiology. Subjects will then be randomized to six months of treatment with zileuton or azathioprine/prednisone. The primary endpoint of this trial is change in LTB4 levels in bronchoalveolar lavage fluid following six months of treatment. Secondary endpoints are progression free survival, change in dyspnea, change in quality of life, and change in physiology.
NCT00262405 ↗	Zileuton for the Treatment of Idiopathic Pulmonary Fibrosis	Completed	University of Michigan	Phase 2	2001-01-01	Open label trial of zileuton compared to azathioprine/prednisone for patients with idiopathic pulmonary fibrosis. Study subjects will undergo a detailed clinical, radiographic, and physiologic assessment at baseline. Subjects will be monitored off treatment for three months for changes in symptoms and physiology. Subjects will then be randomized to six months of treatment with zileuton or azathioprine/prednisone. The primary endpoint of this trial is change in LTB4 levels in bronchoalveolar lavage fluid following six months of treatment. Secondary endpoints are progression free survival, change in dyspnea, change in quality of life, and change in physiology.

Clinical Trial Conditions for zileuton

Condition Name

Condition Name for zileuton
Intervention	Trials
Asthma	6
Lung Cancer	2
Chronic Myelogenous Leukemia	2
Tobacco Use Disorder	2

Condition MeSH

Condition MeSH for zileuton
Intervention	Trials
Asthma	6
Leukemia, Myeloid	2
Leukemia, Myelogenous, Chronic, BCR-ABL Positive	2
Lung Neoplasms	2

Clinical Trial Locations for zileuton

Trials by Country

Trials by Country for zileuton
Location	Trials
United States	75
Brazil	1
India	1

Trials by US State

Trials by US State for zileuton
Location	Trials
Massachusetts	9
California	6
Michigan	5
Minnesota	4
Maryland	4

Clinical Trial Progress for zileuton

Clinical Trial Phase

Clinical Trial Phase for zileuton
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	2
Phase 2	7

Clinical Trial Status

Clinical Trial Status for zileuton
Clinical Trial Phase	Trials
Completed	14
Terminated	5
Unknown status	1

Clinical Trial Sponsors for zileuton

Sponsor Name

Sponsor Name for zileuton
Sponsor	Trials
National Cancer Institute (NCI)	4
Critical Therapeutics	4
University of Massachusetts, Worcester	2

Sponsor Type

Sponsor Type for zileuton
Sponsor	Trials
Other	15
Industry	8
NIH	7

Zileuton (Zyflo) Clinical Trials Update, Market Analysis, and Projection

Last updated: April 27, 2026

What is zileuton’s current clinical and regulatory footprint?

Zileuton is a 5-lipoxygenase inhibitor used for the prevention of asthma symptoms in patients where symptoms are driven by leukotrienes. In practice, it has remained a legacy oral option with limited recent trial volume versus newer asthma classes (inhaled biologics, IL-4Rα, IL-5 axis) and newer oral small molecules.

Key product/regulatory facts

Item	Details
Drug	Zileuton
Brand history	Zyflo and Zyflo CR (extended release) in multiple markets
Class	5-lipoxygenase inhibitor (leukotriene pathway)
Indication (label basis)	Prevention of bronchospasm in asthma patients; used for leukotriene-mediated disease patterns

Source basis: Drug label and historical regulatory framing are consistent across standard reference sources for zileuton. [1][2]

Clinical trials update (signal level)

Across public registries and the medical literature record, zileuton’s trial activity is dominated by:

• Older pivotal programs that supported original approvals.
• Postmarketing studies focused on safety, liver enzyme monitoring, and adherence to contraindication and risk-management elements.
• Periodic, smaller studies that typically do not match the scale or cadence of trials seen for more modern asthma biologics or newer leukotriene pathway candidates.

The net effect for decision-making is that zileuton’s evidence base is mature, and the risk-adjusted probability of near-term label expansion is constrained by the relatively low volume of new, high-impact late-stage programs.

Source basis: Public regulatory and label-centric safety frameworks, with leukotriene-pathway usage context. [1][2]

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What is driving the market for zileuton?

Zileuton competes in a crowded asthma control environment where payers and clinicians prioritize:

• Inhaled controller regimens (ICS and ICS/LABA) and device-based adherence.
• Oral leukotriene receptor antagonists (LTRAs) as common add-on therapy.
• Escalation to biologics or targeted oral agents in severe disease cohorts.

Competitive positioning

Competitive set	Where zileuton loses share	Where it holds
ICS-based step therapy	Oral alternatives face substitution pressure from inhaled controllers	Niche in leukotriene-driven phenotypes
LTRAs (e.g., montelukast class)	Simpler safety management and entrenched use	Patients already stable on leukotriene modulation
Biologics (anti-IL-5/IL-4R/IgE)	Higher efficacy in severe T2 inflammation; payer pathways established	Not a direct overlap in mild-to-moderate segments
Newer oral small molecules	Broader marketing and trial momentum	Limited overlap unless patients are refractory to standard care

Core commercial headwind: zileuton requires adherence to hepatotoxicity risk management and monitoring practices, which increases operational friction for prescribers and payers relative to many alternatives. [1][2]

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How does safety and monitoring shape access and reimbursement?

Zileuton’s safety profile is dominated by liver enzyme elevations and hepatotoxicity risk, which affects:

• Prescribing comfort and clinician adoption.
• Pharmacy and prior authorization friction where payer policies require documentation of baseline liver function.
• Ongoing monitoring workflows.

Liver risk controls on label

Zileuton labeling includes requirements for liver-related monitoring, including baseline assessment and periodic liver function tests, and avoidance in certain patient populations with liver disease. [1][2]

Commercial consequence: higher monitoring costs and increased risk management overhead can reduce the addressable market in real-world formularies versus lower-friction oral options.

Source basis: Label safety and monitoring framework. [1][2]

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What is the market opportunity size and near-term demand profile?

Demand profile

Given the legacy status of zileuton and the competitive landscape, market demand tends to be:

• Stable but not growth-led.
• More dependent on retention in established formularies than on new penetration.
• Concentrated in regions where oral leukotriene-directed options remain used for mild-to-moderate asthma or add-on therapy.

Market growth outlook

For zileuton, the most probable commercial trajectory is:

• Low-to-moderate unit growth tied to patient retention, with periodic switching within leukotriene pathway classes.
• Limited category expansion unless a new formulation, indication, or differentiated clinical evidence emerges.

This is consistent with the pattern seen in mature oral asthma controller candidates that do not have current high-scale development pipelines.

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What is the projection for revenue and market share?

Because zileuton is an older, label-stable asset, projections are best framed as scenario bands driven by three variables: 1) formularies (retention vs substitution to LTRAs and inhaled controllers), 2) patient monitoring burden (adherence and discontinuation), 3) pipeline disruption (new label expansions by competitors or new leukotriene candidates).

Projection framework (scenario-based)

Scenario	Assumptions	Expected direction
Base case	Formularies retain zileuton in a modest set of plans; no major new late-stage clinical data; ongoing monitoring continues to constrain adoption	Flat-to-low growth, slow share bleed
Downside	Continued payer/formulary substitution toward LTRAs/inhaled controller optimization; discontinuation driven by monitoring burden	Declining revenue and share
Upside	New evidence supports safety or a niche expansion, or procurement shifts favor older oral options in resource-limited settings	Stabilization then modest growth

Near-term market trajectory (12–36 months)

• Probability-weighted expectation: flat to modest decline in share with stable pricing pressure.
• Unit volumes: likely stable with gradual erosion where clinicians shift to simpler oral alternatives or preferred inhaled regimens.
• Pricing: constrained by older product status and payer scrutiny.

This projection is aligned with the absence of high-intensity late-stage development momentum for new label expansion in the public record, paired with entrenched competitive alternatives.

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Where are the highest-value development or lifecycle levers?

1) Safety and monitoring simplification

• Any approach that reduces the monitoring burden without compromising risk controls is a direct adoption lever.
• Clinical programs that generate evidence of real-world adherence and safe continuation could improve persistence and reduce discontinuations.

2) Differentiation by asthma phenotype

• Zileuton’s biological target supports potential phenotype-driven use.
• The highest value would come from re-specifying population selection toward leukotriene-driven disease patterns where clinicians can justify oral pathway targeting versus generic add-on use.

3) Formulation and adherence

• Extended release and regimen simplification remain practical levers for adherence.
• Improved tolerability and reduced pill burden can influence discontinuation rates, even without label expansion.

Source basis for risk controls and clinical utility context: label safety and monitoring requirements. [1][2]

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Key takeaways

• Zileuton is a mature, legacy asthma controller with an evidence base anchored in older pivotal programs and label-driven risk controls.
• Market dynamics favor lower-friction alternatives, especially LTRAs and inhaled controller optimization, which cap zileuton’s growth ceiling.
• Hepatotoxicity monitoring requirements constrain adoption and payer/formulary flexibility, shaping a stable but limited demand profile.
• Probabilistic near-term outlook favors flat-to-low growth in units with slow share erosion in competitive asthma formularies unless lifecycle differentiation emerges through safety, monitoring simplification, or phenotype-focused evidence.

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FAQs

1. Is zileuton still used in current asthma practice?
   Yes, but it is typically confined to specific formularies and patient subgroups where clinicians select leukotriene-pathway targeting and can support required monitoring workflows. [1][2]

2. What is the biggest risk driver for zileuton adoption?
   Liver enzyme monitoring and hepatotoxicity risk management requirements, which increase operational friction versus many alternatives. [1][2]

3. Does zileuton face direct competition from newer asthma biologics?
   In severe asthma cohorts, biologics dominate escalation pathways, limiting zileuton’s addressable growth to milder disease segments and specific leukotriene-driven patterns. [1][2]

4. What would most likely increase zileuton’s commercial performance?
   New clinical evidence that enables broader or more efficiently managed use, especially if it reduces monitoring burden or tightens patient-selection criteria. [1][2]

5. Is the clinical development pipeline for zileuton active at high intensity?
   Public evidence indicates mature, label-centered studies rather than a sustained late-stage, high-scale pipeline comparable to newer asthma platforms. [1][2]

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References

[1] Zyflo (zileuton) prescribing information. US FDA label; safety monitoring and liver-related contraindications.
[2] Zyflo CR (zileuton extended-release) prescribing information. US FDA label; monitoring requirements and hepatic warnings.