Clinical Trials and Emerging Treatments for Chronic Aspergillosis

Last reviewed: 12 March 2026

Overview

Treatment options for aspergillosis have improved over time, but there are still important limitations. Only a small number of antifungal drug classes are available, some fungi develop resistance to existing medicines, and some patients cannot tolerate treatment because of side effects or drug interactions.

This is particularly important in chronic aspergillosis, where treatment may need to continue for months or years. Research is therefore focused not only on new antifungal drugs, but also on better drug delivery systems, immune-based treatments, biologic therapies and combinations of treatments.

Clinical trials are the main way that researchers test whether these new approaches are safe and effective.

Why new treatments are needed

New treatments for chronic aspergillosis are needed for several reasons:

• the number of available antifungal drug classes is limited,
• Aspergillus can develop resistance to azole antifungals,
• some patients experience significant side effects or important drug interactions,
• long-term treatment can be difficult to sustain,
• chronic disease may continue to affect symptoms, lung function and quality of life even when treatment is helping.

Because chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and related conditions can behave differently, researchers are exploring a wider range of therapies than in the past.

How new treatments are developed

Before a new treatment can be used routinely, it must pass through several stages of development.

Stage	Description
Basic research	Scientists study the disease and identify targets that could be affected by a new drug or treatment approach.
Drug discovery	Researchers screen chemical compounds or modify promising molecules to find potential treatments.
Pre-clinical studies	Potential treatments are tested in laboratory systems and sometimes animal models to assess activity and safety.
Application to begin human trials	Researchers apply to regulators and ethics committees for permission to test the treatment in people.

Clinical trial phases

Clinical trials are usually carried out in phases.

Phase	Purpose
Phase 0 / Phase I	Small studies, often in healthy volunteers, to understand how the treatment behaves in the body, including absorption, distribution and safe dose ranges.
Phase II	Studies in patients with the disease to identify useful doses and gather early information on effectiveness and side effects.
Phase III	Larger studies comparing the new treatment with existing care to assess effectiveness and safety more accurately.
Phase IV	Post-marketing studies that monitor how the treatment performs in real-world use after approval.

Regulatory approval and NHS use

If a treatment performs well in trials, the manufacturer can apply for approval from a medicines regulator such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA).

In the United Kingdom, a treatment may also be assessed by the National Institute for Health and Care Excellence (NICE) to determine whether it should be funded for routine use in the NHS.

Even when a drug is not recommended for routine NHS use, doctors may sometimes apply for individual funding if they believe it could benefit a particular patient.

New antifungal drugs in development

Many new antifungal drugs are first developed for severe invasive fungal infections and may later be studied in chronic conditions such as CPA or ABPA.

Olorofim

Olorofim is a novel antifungal from a completely new class called the orotomides. It targets fungal pyrimidine synthesis, a pathway not affected by current azole, echinocandin or polyene antifungals.

Rezafungin

Rezafungin is an echinocandin designed to have a longer duration of action and improved pharmacokinetic properties compared with older drugs in the same class.

Ibrexafungerp

Ibrexafungerp belongs to a new group of antifungals called triterpenoids. It acts on fungal cell wall synthesis in a way that is similar to echinocandins, but its structure is different and it can be given orally.

Fosmanogepix

Fosmanogepix is a first-in-class antifungal that blocks production of a molecule needed for fungal cell wall construction and self-regulation.

Oteseconazole

Oteseconazole is one of the newer tetrazole agents designed to improve selectivity and reduce side effects compared with traditional azoles.

Encochleated Amphotericin B

This is a reformulated version of amphotericin B designed to improve delivery and reduce toxicity.

ATI-2307

ATI-2307 is an arylamidine antifungal that interferes with mitochondrial function in fungal cells.

Other emerging treatments for chronic aspergillosis

Although new antifungal drugs are an important area of research, scientists are also exploring other ways to treat chronic forms of aspergillosis such as chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). These approaches aim to improve treatment effectiveness, reduce side effects, or target the immune response to the fungus.

Inhaled antifungal treatments

One area of research is the development of antifungal medicines that can be delivered directly to the lungs using inhalers or nebulisers. Delivering medication directly to the lungs may allow higher drug concentrations at the site of disease while reducing side effects elsewhere in the body.

Examples being explored include inhaled or nebulised formulations of amphotericin B, itraconazole and voriconazole.

Immune-modulating therapies

In some patients with aspergillosis, the immune response to the fungus plays an important role in how the disease develops or persists. Researchers are studying treatments that help modify the immune response rather than directly killing the fungus.

Examples include therapies that may enhance antifungal immunity or reduce harmful inflammation.

Biologic therapies

Biologic drugs that target specific immune pathways are already used to treat severe asthma and allergic disease. Some of these medicines are now being studied or used in fungal-related airway disease.

Examples include drugs targeting immunoglobulin E (IgE) or eosinophilic inflammation, such as omalizumab, mepolizumab, benralizumab, dupilumab and tezepelumab. These may be particularly relevant in ABPA or severe asthma with fungal sensitisation (SAFS).

Combination therapies

Future treatment strategies may combine different approaches, for example antifungal medication together with biologic therapy, inhaled therapy or immune-modulating treatment. Combination treatment may improve outcomes in patients whose disease does not respond fully to a single treatment alone.

Research is ongoing to determine which combinations are most effective and safest for patients with chronic aspergillosis.

Why new treatments are often tested in invasive aspergillosis first

Many new antifungal drugs are first tested in patients with invasive aspergillosis before being studied in chronic forms of the disease such as chronic pulmonary aspergillosis (CPA) or allergic bronchopulmonary aspergillosis (ABPA).

There are several reasons for this:

• Disease progression is faster. In invasive infections the illness progresses quickly, so researchers can more easily measure whether a new treatment is working.
• Clearer treatment outcomes. Invasive infections often have well-defined clinical outcomes such as survival or clearance of infection.
• Smaller studies can provide useful results. Because invasive infections are severe, treatment effects may be detected in smaller numbers of patients.

Chronic forms of aspergillosis usually progress more slowly. This means clinical trials often need to run for longer periods and include larger numbers of patients to demonstrate whether a treatment is effective.

Once a new antifungal drug has shown benefit in invasive disease, researchers may then study how it performs in chronic conditions such as CPA or ABPA.

Specialist centres such as the National Aspergillosis Centre contribute to research that helps evaluate new treatments for chronic forms of aspergillosis and improve care for patients living with these conditions.

How to find clinical trials

Clinical trials involving human participants must be registered publicly for ethical and regulatory reasons.

You can search for ongoing or completed studies at:

• ClinicalTrials.gov

This database allows you to search for studies by disease, location, treatment or trial status.

Not all studies test new drugs. Some trials investigate diagnostics, biomarkers, new ways of using existing medicines, or observational registries that help researchers understand disease patterns over time.

If you are interested in taking part in a clinical trial, discuss this with your specialist respiratory team.

Common questions

Why are new treatments needed if antifungal drugs already exist?

Current antifungal drugs help many patients, but they do not work for everyone. Some fungi develop resistance, some patients experience side effects or interactions, and chronic disease can remain difficult to control.

Are all new treatments new antifungal drugs?

No. Research now includes new antifungal drugs, inhaled treatments, biologics, immune-modulating therapies and combination approaches.

Why are there more trials in invasive aspergillosis than CPA?

Invasive aspergillosis progresses more quickly, so trial results can often be measured sooner and with fewer patients. CPA usually changes more slowly, which makes trials longer and more difficult to run.

Can patients with chronic aspergillosis join clinical trials?

Sometimes, yes. Eligibility depends on the trial design, the type of aspergillosis, previous treatment and other health factors. Your specialist team can advise whether there may be suitable studies.

Do clinical trials always involve testing a completely new drug?

No. Some studies test new doses, new combinations, new formulations such as inhaled treatment, or new diagnostic approaches.

Further information

You may find these pages helpful:

• Antifungal medicines for aspergillosis
• Biologics and eosinophilic asthma
• Inhalers and nebulisers
• Chronic pulmonary aspergillosis (CPA)
• Allergic bronchopulmonary aspergillosis (ABPA)

More information about the medicine development process can be found through major medicines regulators, clinical trial registries, and specialist respiratory teams.

Author and review information

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