CLINICAL TRIALS PROFILE FOR VORICONAZOLE

505(b)(2) Clinical Trials for voriconazole

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Dosage	NCT00421187 ↗	Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics	Terminated	Gilead Sciences	Phase 4	2007-03-01	Administration of a single high dose (10 mg/kg) of AmBisome® no later than 72 hours after ARNF onset followed by two 5 mg/kg doses on days 2 and 5 may provide sustained tissue levels of amphotericin B that are as mycologically effective as those provided after administering the standard daily dose of 3 mg/kg/day. The new dosing regimen is anticipated to be equally clinically effective compared with the standard AmBisome® regimen when given for the duration of neutropenic fever in patients with ARNF. In addition, the degree and incidence of nephrotoxicity are predicted to be lower with the 3 sequential dose regimen compared to daily dosing with 3 mg/kg because of the lower cumulative dosage (20 mg/kg versus 42 mg/kg, respectively), which is 1 contributing factor for the development of acute renal failure. Furthermore, the lower cumulative dose may be a cost-effective strategy for the treatment of patients with ARNF.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Institutul Clinic Fundeni	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Institutul Clinic Fundeni Bucharest	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Universitaire Ziekenhuizen Leuven	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.

All Clinical Trials for voriconazole

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001646 ↗	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1997-08-01	Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B. Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the US. This azole has been shown active against Aspergillus spp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation. This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio.
NCT00001757 ↗	An Open Label, Non-Comparative, Multicenter, Phase III Trial of the Efficacy, Safety and Toleration of Voriconazole in the Primary or Secondary Treatment of Invasive Fungal Infections	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1997-11-01	Invasive fungal infections are often life-threatening in persons with immunocompromise. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at high risk for these infections. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. With the use of currently approved antifungal therapy, many of these infections may still be associated with a high mortality. Amphotericin B in its conventional form, is the current standard treatment for most life-threatening fungal infections. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. Alternated agents include three lipid formulations of amphotericin B, fluconazole, itraconazole. Although all of these agents are associated with a decrease in adverse effects, their efficacy in most life-threatening fungal infections has not been shown to be equivalent to conventional amphotericin B. Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the US. This azole has been shown active against many fungal pathogens in vitro. In animal models and early human trials this new agent has been shown to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation. This is a non-comparative, open label study to evaluate the efficacy, safety and toleration of voriconazole in the treatment of invasive fungal infections. This agent will be used as primary therapy in those fungal infections in which no antifungal agent is currently approved or in patients unable to tolerate the approved agent. Voriconazole will also be used as a secondary treatment in those patients who have failed therapy with the primary approved agent or are unable to tolerate that agent or have unacceptable toxicity.
NCT00001810 ↗	An Open Label, Non-Comparative, Multicenter, Phase III Trial of the Efficacy, Safety and Toleration of Voriconazole in the Primary or Secondary Treatment of Invasive Fungal Infections	Completed	National Cancer Institute (NCI)	Phase 3	1999-04-01	The objective of this study is to evaluate the efficacy, safety and toleration of voriconazole in the primary treatment of systemic or invasive fungal infections due to fungal pathogens for which there is no licensed therapy; and in the secondary treatment of systemic or invasive fungal infections in patients failing or intolerant to treatment with approved systemic antifungal agents. This trial is a Phase II multicenter, open label study investigating the utilization of voriconazole for the treatment of systemic or invasive fungal infections. Enrollment is targeted for 150 patients to be recruited from multiple centers. The patient population will consist of patients with proven, deeply invasive fungal infection for which there is no licensed therapy or if the patient is failing or intolerant to treatment with approved systemic antifungal agents. Voriconazole will be administered initially by a loading dose of 6 mg/kg q12 hours for the first two doses followed by 4 mg/kg q12 hours. Efficacy will be evaluated by clinical, radiological and microbiological response.
NCT00001940 ↗	Voriconazole to Treat Fungal Infections	Completed	National Cancer Institute (NCI)	Phase 3	1999-12-01	Voriconazole is a new drug developed to treat fungal infections. As of March 1999, the drug had been studied in more than 1,900 healthy volunteers or patients with fungal infections. This study will test extended use of voriconazole in patients with serious fungal infections for which there are no approved therapies, and in patients who did not improve with or could not tolerate standard therapy. It will evaluate the drug's safety, effectiveness, and toleration in these patients. Patients previous enrolled in protocol 99-C-0094 who improved with voriconazole treatment are eligible for this study. Before beginning treatment, patients will have a physical examination, including blood and urine tests, and an eye examination. They may also have X-ray or CT imaging. Voriconazole will then be given twice a day either by infusion into a vein or by tablets taken by mouth for up to 12 weeks. Patients will be examined at weeks 4, 8 and 12 of the study and one week after treatment stops. Blood and urine samples will be collected at each visit. An eye examination will be done at the end of the treatment period and at other visits if vision problems develop. Voriconazole is active against fungal infections and may produce fewer side effects than standard therapy.

Clinical Trial Conditions for voriconazole

Condition Name

Condition Name for voriconazole
Intervention	Trials
Aspergillosis	14
Fungal Infection	13
Healthy	9
Leukemia	7

Condition MeSH

Condition MeSH for voriconazole
Intervention	Trials
Mycoses	55
Aspergillosis	36
Infections	21
Infection	20

Clinical Trial Locations for voriconazole

Trials by Country

Trials by Country for voriconazole
Location	Trials
United States	262
India	25
Japan	25
Canada	24
France	21

Trials by US State

Trials by US State for voriconazole
Location	Trials
Texas	23
California	21
Maryland	20
Pennsylvania	13
Ohio	13

Clinical Trial Progress for voriconazole

Clinical Trial Phase

Clinical Trial Phase for voriconazole
Clinical Trial Phase	Trials
PHASE3	1
PHASE2	4
PHASE1	1

Clinical Trial Status

Clinical Trial Status for voriconazole
Clinical Trial Phase	Trials
Completed	104
Recruiting	19
Terminated	15

Clinical Trial Sponsors for voriconazole

Sponsor Name

Sponsor Name for voriconazole
Sponsor	Trials
Pfizer	35
National Cancer Institute (NCI)	12
University of California, San Francisco	5

Sponsor Type

Sponsor Type for voriconazole
Sponsor	Trials
Other	165
Industry	76
NIH	27

VORICONAZOLE Clinical Trials Update, Market Analysis, and Patent-Driven Projection for Exclusivity and Generic Entry

Last updated: July 23, 2026

Voriconazole is an orally and intravenously administered triazole antifungal used for invasive aspergillosis and serious fungal infections including fluconazole-resistant candidiasis in many geographies. The drug has mature clinical evidence and a long commercialization history, so near-term market trajectory is driven mainly by (1) hospital formulary access and drug acquisition costs, (2) uptake of alternative antifungals, (3) antimicrobial stewardship restrictions, and (4) generic competition risk where patent coverage is expired or weak by jurisdiction.

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What phase 3 and real-world clinical evidence is most current for voriconazole?

Bottom line: Clinical development updates for voriconazole are largely incremental: safety, therapeutic drug monitoring (TDM), pharmacokinetics (PK), and comparisons versus other mold-active azoles (posaconazole, isavuconazole) and echinocandins. The active “trial” landscape is dominated by observational studies, PK/TDM optimization protocols, and post-authorization comparative effectiveness rather than new registrational phase 3 programs.

Which clinical trial directions are getting the most study volume?

1. Therapeutic drug monitoring (TDM) and exposure-response
   • Goal is to reduce treatment failures from underexposure and toxicity from overexposure (notably neurotoxicity and hepatotoxicity).
   • Common endpoints: trough concentrations, time-in-therapeutic range, adverse event rates, and mortality/morbidity.
2. Dosing optimization in special populations
   • Adult and pediatric pharmacokinetics.
   • ICU, hepatic impairment, and renal function changes.
   • Drug-drug interaction management because voriconazole is metabolized by CYP2C19 and affected by CYP interactions.
3. Switching strategies and route comparisons
   • IV-to-oral step-down strategies.
   • Loading/maintenance regimens tailored to institutional protocols.
4. Comparative effectiveness in invasive mold disease
   • Real-world cohorts comparing outcomes with isavuconazole or posaconazole where voriconazole is a comparator arm or control group.

Where does voriconazole still perform in clinical practice?

• Mold-active first-line/alternative therapy for invasive aspergillosis.
• Salvage therapy in selected cases where resistance, intolerance, or availability favors voriconazole.
• Settings where TDM is available and clinicians manage CYP interactions.

Clinical trial “update” implication for forecasting

Because registrational late-stage pipeline activity is limited, market momentum is tied to:

• How quickly formularies adopt newer azoles and echinocandins as preferred options.
• Whether TDM infrastructures improve outcomes and reduce discontinuation rates for voriconazole.
• Margin pressure from generic entry, where it is already underway or expected.

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How big is the voriconazole market and what segment is driving demand?

Bottom line: Demand is primarily hospital-based. Use is concentrated in tertiary centers treating invasive fungal disease, with additional pull from ICU and oncology settings. Market growth is modest; volume is stable to slightly down in mature markets due to alternative agents and stewardship policies, while emerging market growth is more about baseline penetration and infrastructure.

Market segmentation that matters for revenue projection

• Indication-driven demand
  • Invasive aspergillosis is the central mold indication.
  • Serious candidiasis and off-label use contribute in some systems.
• Route
  • IV dominates severe disease initial management in many hospitals.
  • Oral accounts for step-down therapy once patients stabilize.
• Geography
  • Mature Western markets have strong generic penetration.
  • Higher-growth regions depend on reimbursement stability and antimicrobial program maturity.
• Hospital formulary rules
  • Inclusion often hinges on stewardship and TDM availability.

Revenue projection levers

Forecasts for voriconazole usually hinge on a small set of variables:

1. Unit price erosion from generics.
2. Utilization shift toward isavuconazole/posaconazole and echinocandin strategies.
3. Exclusivity and patent posture that may still protect certain brands or formulations in select jurisdictions.
4. Reimbursement dynamics and procurement contracting.

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When does voriconazole lose exclusivity, and how does that affect generic entry risk?

Bottom line: For most major markets, voriconazole’s core active-substance exclusivity has long since expired. The residual IP risk, and therefore time-to-generic pressure, is usually from formulation-specific patents, manufacturing-process patents, and jurisdiction-specific secondary patents rather than the original drug itself.

What drives “last mile” exclusivity in voriconazole?

• Drug product/formulation patents
  • Extended-release is not the main story for voriconazole; protections tend to be around specific dosage forms, excipients, and stability.
• Manufacturing and process patents
  • Scale-up, impurity profile targets, and specific process controls can delay certain generic approvals in narrow cases.
• Therapeutic drug monitoring-related claims
  • “Method of use” claims can exist in some estates but are harder to enforce against standard-of-care prescribing once generic labeling is aligned.

Generic entry scenario for forecasting

• In jurisdictions with expired active substance patents and no enforceable product/process patents, generic erosion is typically already realized and becomes a steady-state margin problem rather than a step-change.
• In jurisdictions where late blocking patents exist, generic entry may arrive later but still cause a sharp price reset after lifting of litigation/injunction.

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What patents protect voriconazole in key jurisdictions, and where are the strongest estates?

Bottom line: The meaningful IP now is typically secondary patents and legacy formulation/process protections, often narrower than the original compound coverage. Strongest protection is expected where brands have maintained technical differentiation and where litigation created settlement constraints.

What patent categories are most likely to appear in voriconazole estates

1. Formulation and composition of matter for dosage forms
   • Tablets and IV formulations, stability and impurity control, excipient systems.
2. Manufacturing process claims
   • Specific steps that control impurities or particle attributes.
3. Method-of-use claims
   • Dosing algorithms tied to TDM targets.
4. Medical device or diagnostic pairing
   • Less common for voriconazole itself, but may appear in broader antifungal TDM approaches.

How to use patent strength for market forecasting

• Strong estate in a jurisdiction increases the expected duration of premium pricing and reduces generic substitution.
• Weak estate increases the speed and magnitude of ASP declines after entry.

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What patent litigation affects voriconazole generics, including Paragraph IV and settlements?

Bottom line: Patent litigation in voriconazole historically included generics contesting secondary patents and brand-holder claims in the US. The current practical effect on forecasting is whether any active injunction or settlement restraint exists in major markets, because that controls timing of additional generic entrants and batch supply.

Litigation mechanics that drive market timelines

• Paragraph IV filings (US)
  • Block generic launch until patent resolution or settlement.
• Settlement agreements
  • Can impose “design-around” or timing restrictions.
• Injunctions
  • Shorten to resolution date if overturned; extend if upheld.
• Labeling carve-outs
  • Sometimes allow entry for certain strengths or routes while keeping other presentations locked.

Forecast implication

If a jurisdiction has no active restrictions, market pricing behaves like a commodity: ASP declines continue until competitive equilibrium.

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What is the Orange Book status of voriconazole, and how many listed patents are relevant?

Bottom line: The Orange Book typically shows a mix of expired and active listings for drug products. The practical forecasting value is current “listed but unexpired” patents (or those tied to an unexpired regulatory exclusivity or settlement-imposed constraint). For many established products, the number of active listings is small relative to historical counts.

What to look for on Orange Book for forecast modeling

• Unexpired drug product patents
• Unexpired method-of-use patents
• Unexpired exclusivity codes
• Whether listed patents have been carved out by litigation outcomes
• Whether generics can launch for some strengths/routes

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How does voriconazole compare with isavuconazole and posaconazole on market and clinical adoption?

Bottom line: Market share shifts are driven by administration convenience, safety tolerability profiles, drug interaction handling, and formulary preference. Isavuconazole has been a consistent challenger where clinicians prefer its dosing and safety profile. Posaconazole is used broadly for prophylaxis and treatment in many protocols. Voriconazole remains important for invasive aspergillosis where clinicians have confidence in TDM-based management.

Commercial and clinical adoption drivers

• Safety management
  • Voriconazole’s adverse event profile is manageable with TDM but can deter use in settings without monitoring.
• Drug-drug interaction burden
  • All azoles interact, but voriconazole’s CYP2C19 metabolism and clinical practice experience drive careful stewardship.
• Prophylaxis vs treatment use
  • Posaconazole often captures prophylaxis protocol budgets, which can indirectly compress voriconazole treatment volumes.
• Guideline dynamics
  • Local guideline updates can tilt usage between agents.

Forecast implication

• If newer azoles keep displacing voriconazole in first-line mold therapy or prophylaxis ecosystems, volume growth will be flat while price declines continue under generic pressure.
• If voriconazole remains the “TDM-supported workhorse” for confirmed aspergillosis, decline may slow relative to markets where alternatives dominate.

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What generic entry risks exist for voriconazole by dosage form and route?

Bottom line: Generic entry risk is highest for widely used strengths and routes where patent protection has expired and manufacturing/process patents do not block approval. For IV products, supply chain and formulation stability requirements can make entry slower or less reliable, but once approved, price competition accelerates.

Dosage form risk map (how to structure forecasting)

• Oral tablets
  • High substitution risk once patents and exclusivity barriers are gone.
• IV formulation
  • Potentially slower penetration due to formulation complexity, but once multiple suppliers exist, ASP erosion follows.
• Strength-specific risk
  • Some strengths may retain narrow protections or face longer “stability/impurity” qualification timelines.

Manufacturing/IP barriers to entry

• Impurity specifications and shelf-life stability for IV solutions can be gating factors.
• Any residual manufacturing-process patents can delay competition in narrow cases.

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Regulatory pathway considerations: will new voriconazole approvals change the market?

Bottom line: In established drugs, regulatory events rarely create “step-change” demand unless they:

• Introduce a significantly differentiated product form, or
• Expand approved indications in a way that meaningfully alters prescribing behavior.

For voriconazole, most “regulatory activity” in mature markets is expected to be generic approvals and labeling updates rather than new product launches.

Pathway mechanics that affect pricing timelines

• ANDA approvals
  • Typically increase supply and accelerate price erosion.
• Labeling negotiations
  • Can restrict interchangeability for specific patient populations or routes.
• Safety labeling updates
  • Can tighten prescribing rules and reduce eligible use, partially offsetting generic-driven volume gains.

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Market projection for voriconazole: base case, downside, and upside scenarios

Bottom line: A robust model uses three drivers: (1) unit price after generic entry, (2) utilization trend driven by substitution to newer azoles, and (3) any remaining jurisdiction-level IP friction.

Base case (most likely in mature markets)

• Generic-driven price erosion continues.
• Volume is stable or slightly down due to competitive substitution.
• Share loss is gradual; major hospital formularies already have access to alternatives.

Downside case

• Faster substitution to isavuconazole/posaconazole and guideline tightening reduces treatment share for voriconazole.
• Smaller hospitals and stewardship programs limit azole switching to TDM-supported centers, reducing eligible patient counts.

Upside case

• Improved TDM protocols reduce discontinuations and improve outcomes, supporting continued use in invasive aspergillosis.
• Drug shortages or supply constraints among alternatives temporarily support voriconazole purchasing.

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Key Takeaways

• Voriconazole clinical “updates” are largely TDM, PK optimization, special-population safety, and real-world comparative effectiveness rather than new registrational late-stage trials.
• Market trajectory is driven less by R&D breakthroughs and more by generic price erosion and substitution to isavuconazole/posaconazole in invasive mold pathways.
• Exclusivity timing is typically dominated by expired core active-substance coverage; remaining jurisdictional impact is usually from secondary formulation/process and any unsettled litigation constraints.
• Forecasting should be built around route- and strength-level generic entry timelines and the persistence of any active Orange Book listings or settlement-enforced launch delays.
• The highest forecasting sensitivity is to hospital formulary behavior and stewardship rules that determine which centers can use voriconazole with TDM.

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FAQs

1. Does therapeutic drug monitoring increase voriconazole survival outcomes versus fixed dosing?
2. How do safety labeling changes for voriconazole affect prescribing volume in antifungal stewardship programs?
3. Which patient subgroups have the highest expected benefit or risk from voriconazole compared with isavuconazole?
4. Do generic voriconazole manufacturers differ meaningfully in impurity profiles or IV formulation stability?
5. What are the most common reasons for switching from voriconazole to another antifungal during invasive aspergillosis treatment?

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References (APA)

1. [No sources were provided in the prompt for Orange Book, FDA label history, trial registries, or market datasets; therefore, no citations can be listed.]