GAtherton

Developments in Biologic and Inhaled Antifungal medications for ABPA

Updated October 2026

Treatment for allergic bronchopulmonary aspergillosis (ABPA) is changing. Oral corticosteroids and oral antifungal drugs remain important treatments, but newer approaches aim to control the allergic inflammation caused by Aspergillus while reducing the problems associated with repeated or long-term steroid and antifungal treatment.

Two areas are attracting particular interest: biologic medicines, which target specific parts of the immune response, and inhaled antifungal treatments, which aim to deliver antifungal drugs directly to the lungs.

Neither has replaced conventional ABPA treatment, but the evidence supporting these approaches has developed considerably in recent years.

Key points

• Oral corticosteroids and itraconazole remain established treatments for acute ABPA.
• Biologics are increasingly used in selected people with recurrent or treatment-dependent ABPA, particularly where reducing exposure to oral corticosteroids is important.
• Omalizumab, mepolizumab and benralizumab currently have the largest body of clinical experience in ABPA, with emerging evidence for dupilumab and other biologics.
• There is not yet enough evidence to identify one biologic as the best treatment for ABPA or to establish an optimal sequence.
• Inhaled antifungals aim to achieve high antifungal concentrations in the lungs while reducing systemic exposure.
• A 2026 phase 2 trial of inhaled itraconazole (PUR1900) produced encouraging results, but larger phase 3 trials are needed.
• Opelconazole is another investigational inhaled antifungal of interest.

Where does treatment for ABPA stand now?

The 2024 international ISHAM guidelines for ABPA recommend oral prednisolone or itraconazole alone for treating acute ABPA, whether newly diagnosed or an exacerbation. Combination treatment with prednisolone and itraconazole is generally reserved for recurrent exacerbations rather than being used routinely as initial treatment.

The guidelines do not recommend biologics as routine first-line treatment for acute ABPA. However, biologics have an increasingly important potential role in people with treatment-dependent or recurrent disease, particularly when repeated courses or long-term use of corticosteroids are causing problems.

This distinction is important. Biologics are not simply newer replacements for steroids or antifungal drugs: they target a different part of the disease process.

Why might biologics help in ABPA?

ABPA involves an exaggerated immune response to Aspergillus in the airways. This commonly involves type 2 inflammation, including IgE, eosinophils and signalling pathways involving cytokines such as IL-4, IL-5 and IL-13.

Biologic medicines can selectively interfere with these pathways. Several biologics originally developed for severe asthma have therefore been used in people with ABPA.

Omalizumab

Omalizumab targets IgE and has the longest history of biologic use in ABPA.

Clinical experience and observational studies suggest that some people experience fewer exacerbations, improved asthma control and reduced dependence on oral corticosteroids.

ABPA can, however, produce extremely high IgE concentrations, sometimes outside conventional dosing ranges used for severe allergic asthma.

Mepolizumab and benralizumab

Mepolizumab targets IL-5, while benralizumab targets the IL-5 receptor and produces marked depletion of eosinophils. Both have been used in ABPA, particularly when eosinophilic inflammation and severe asthma are prominent features.

A 2025 real-world study of 74 people with ABPA receiving biologic therapy found that 65% were considered to have responded successfully at 12 months, with improvements in asthma control and exacerbation frequency and reduced maintenance oral corticosteroid use.

However, 35% stopped or changed biologic during follow-up, principally because of an inadequate clinical response. This illustrates an important point: biologics can work very well for some people with ABPA, but not everyone responds.

Dupilumab

Dupilumab blocks signalling through the IL-4 receptor alpha pathway, affecting both IL-4 and IL-13 signalling.

Case reports and observational experience have described successful treatment of difficult ABPA, including in some people who have not responded adequately to other biologics. However, ABPA-specific evidence remains much less extensive than we would ideally want when deciding which biologic should be used for an individual patient.

Tezepelumab

Tezepelumab targets thymic stromal lymphopoietin (TSLP), an upstream signalling molecule involved in airway inflammation.

It is an established treatment for some people with severe asthma, and there are reports of its use in ABPA, but evidence specifically for ABPA remains limited. Its effectiveness in severe asthma should therefore not be interpreted as proof that it is an established ABPA treatment.

Can patients switch biologics?

Yes. Switching between biologics is increasingly reported when the first treatment produces an inadequate response or causes problems.

A 2026 scoping review of biologic switching in ABPA identified 73 published patients and 108 switching events.

Omalizumab was the most frequently reported initial biologic. Switching from omalizumab to an IL-5 or IL-5-receptor treatment was common, while subsequent switching to dupilumab was also reported.

Many published cases reported improvement after switching. However, most of the evidence consisted of case reports, case series and retrospective observational studies. We therefore cannot yet reliably identify the best biologic for ABPA or establish the best sequence in which biologics should be tried.

Why are inhaled antifungals interesting?

Oral azole antifungals such as itraconazole can reduce the burden of Aspergillus in the airways, but the drug circulates throughout the body.

This can create several difficulties, including:

• drug interactions;
• variable absorption and blood concentrations;
• liver toxicity and other adverse effects;
• the need for therapeutic drug monitoring in many circumstances.

An inhaled antifungal offers an attractive alternative in principle: deliver a high concentration of antifungal directly to the airways while reducing exposure elsewhere in the body.

Achieving this successfully is technically difficult. A formulation must reach the appropriate parts of the lungs, remain active, be tolerated by sensitive or inflamed airways and be delivered consistently by an inhalation device.

Nevertheless, there is now considerably more clinical evidence than when this article was originally written in 2023.

Inhaled itraconazole: PUR1900

One of the most important recent developments is PUR1900, an inhaled formulation of itraconazole designed to produce high concentrations of the drug in the airways with relatively low systemic exposure.

Results from a phase 2 randomised controlled trial of PUR1900 in adults with asthma and ABPA were published in 2026.

The study included 43 participants who received PUR1900 20 mg, PUR1900 40 mg or placebo once daily for 16 weeks.

At 16 weeks, the 40 mg dose was associated with improvements compared with placebo in several exploratory measures, including lung function (FEV₁), asthma control and total IgE. No comparable placebo-adjusted effect was seen with the 20 mg dose. Adverse events were not more frequent with the 40 mg dose than with placebo in this small study.

There is an important limitation: this was a small exploratory phase 2 trial without a prespecified primary endpoint. It therefore does not establish inhaled itraconazole as a standard treatment for ABPA.

However, the findings were sufficiently encouraging to support further phase 3 evaluation. This represents an important advance from the situation in 2023, when we were largely waiting to discover whether this approach could work clinically.

Opelconazole

Another investigational inhaled antifungal is opelconazole, previously known as PC945.

Opelconazole is a triazole designed specifically for inhaled delivery, with the aim of achieving high concentrations in the lungs while limiting systemic exposure.

A 2025 case report described successful treatment of a patient with ABPA using inhaled opelconazole. This is interesting but, as a single case report, cannot establish how effective the treatment will be across the wider ABPA population.

Pharmacology studies are also encouraging. A 2025 study examining the drug-interaction potential of inhaled opelconazole found negligible CYP-mediated interaction potential at the systemic concentrations produced by inhaled treatment.

This illustrates one of the potential advantages of inhaled antifungal treatment: reducing some of the systemic drug-interaction problems associated with oral azoles.

Opelconazole remains investigational and is not routine treatment for ABPA.

What does this mean for patients now?

For most people experiencing a new or acute episode of ABPA, established treatments remain the starting point.

The important change is that clinicians now have a growing range of options to consider when ABPA repeatedly returns, becomes dependent on corticosteroids, conventional treatments cannot be tolerated, or severe asthma and type 2 inflammation are also important components of the person's disease.

Biologics may allow some patients to reduce their exposure to systemic corticosteroids. The largest recent real-world ABPA study provides encouraging evidence for this approach, while also showing that a substantial minority do not respond adequately.

Inhaled antifungals offer a different strategy: targeting Aspergillus in the lungs while attempting to minimise systemic antifungal exposure. The positive phase 2 PUR1900 findings are encouraging, but this approach remains investigational.

Looking ahead

The major unanswered question is no longer simply whether these newer treatments can work. We increasingly need to understand which treatment is most appropriate for which patient.

ABPA is unlikely to behave identically in everyone. Some people may have particularly prominent eosinophilic or IgE-driven inflammation; others may have substantial fungal burden, mucus plugging, bronchiectasis or difficult asthma.

Future studies should help determine whether these characteristics can guide treatment selection between antifungal therapy, biologics and combinations of treatments.

For people with difficult or treatment-dependent ABPA, these developments provide additional treatment possibilities. However, they also reinforce the importance of specialist assessment: the newest treatment is not necessarily the most appropriate treatment for every patient.

Further reading and references

• Agarwal R, et al. (2024). Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.
• Real-World Effectiveness of Biologic Therapy in Allergic Bronchopulmonary Aspergillosis (2025). Study of 74 patients receiving biologic treatment for ABPA.
• Hu Q, et al. (2026). Biologic switching in allergic bronchopulmonary aspergillosis: a scoping review of published clinical experience.
• Agarwal R, et al. (2026). Safety and efficacy of inhaled itraconazole in adults with asthma and ABPA (PUR1900-ABPA): phase 2 randomised controlled trial.
• Nwankwo L, et al. (2025). Successful treatment of an allergic bronchopulmonary aspergillosis patient with inhaled antifungal opelconazole.
• Cass LMR, et al. (2025). In vitro and clinical data demonstrate negligible risk of drug-drug interactions with opelconazole, a novel inhaled antifungal agent.

This information is intended to explain current and emerging treatment approaches and is not a substitute for individual medical advice. Treatment decisions for ABPA should be made with the clinical team responsible for the patient's care.

by GAtherton