💡 Dupilumab for ABPA: What You Need to Know Now the Trial Is Complete

A large Phase III trial—called LIBERTY‑ABPA AIRED—has recently completed studying dupilumab in people with ABPA and asthma who frequently exacerbate despite other treatments. Let’s break down what that means and what’s still missing 📌

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🗓️ Trial Timeline & Scope

• Trial completed: Primary data collection finished in July 2023, study closed in February 2024. It enrolled around 170 patients from over 30 sites across several countries including the UK, EU, US, Canada, Japan, and more Wikipedia+15trialsummaries.com+15Clinical Trials Register+15.

• Design: Randomized, double‑blind, placebo‑controlled over 52 weeks, followed by 12 weeks safety follow‑up trialsummaries.comClinical Trials Register.

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📋 What Was Measured?

The trial assessed:

• Severe respiratory exacerbations (requiring steroids or hospital admission)

• Lung function changes (e.g. FEV₁)

• ABPA-related symptoms, quality of life, asthma control

• Biomarkers including IgE and FeNO

• Safety and tolerability, including antibody formation to dupilumab Wikipedia+15Clinical Trials+15trialsummaries.com+15

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🧬 Why Results Matter

Dupilumab blocks both IL‑4 and IL‑13 pathways, which drive inflammation, mucus, and elevated IgE in ABPA. Early case reports and small series have shown promising benefits, especially in reducing exacerbations and steroid use, but until now, no large randomized trial data were available ScienceDirect+1PMC+1.

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❓ What’s Available Now?

• ✅ The trial has finished, but official results have not yet been published or released publicly.

• 🕒 Regulators and sponsors previously estimated publication around late 2023, with actual report likely still under review or preparation ctv.veeva.com+3ScienceDirect+3Clinical Trials+3.

• 📡 Until these results are public, dupilumab remains not officially approved for ABPA, though individual clinicians may consider off‑label use in select cases.

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🧾 Summary Table: Where Things Stand

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💬 What Should Patients Do Now?

If you’re managing ABPA and considering biologic options:

• ✅ Ask if longstanding biologics like dupilumab are being considered for your individual case.

• 💬 Be clear that formal approval for ABPA is still pending, pending public release of the trial results.

• 🩺 Consult with your specialist or asthma/respiratory team about possible off‑label use—they can explain access options, benefits, and risks.

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🧭 Final Thoughts

The LIBERTY‑ABPA AIRED trial has now completed, marking a major milestone for potential new treatment in ABPA. But until results are published and reviewed, dupilumab remains off-label for this condition.

You may still hear about its use in ABPA from case reports showing positive outcomes—but wider clinical acceptance awaits published study data. If it becomes available, it could offer meaningful benefits—but only if confirmed in research.

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by GAtherton

🔬 Emerging Research for Aspergillosis

Aspergillosis is a complex group of diseases caused by the Aspergillus fungus. Ongoing research is uncovering new ways to diagnose, treat, and prevent these conditions—offering hope for improved care and long-term outcomes. This page outlines current areas of promising research relevant to patients, carers, and healthcare professionals.

⏱️ Has Research Accelerated Over Time?

Yes. Over the last 40 years, research into aspergillosis and fungal infections has significantly accelerated due to:

• Rising awareness of fungal diseases in immunocompromised patients
• Improved diagnostic technology (e.g. PCR, lateral flow tests, next-gen sequencing)
• New drug development in response to growing azole resistance
• Greater investment from both academic institutions and industry
• Dedicated centres like the UK National Aspergillosis Centre driving specialist research
• Fungal infections gaining WHO recognition as emerging public health threats

In the 1980s and 1990s, progress was relatively slow. Since the early 2000s—and especially after the COVID-19 pandemic revealed the risks of fungal co-infection—momentum has increased markedly.

1. 🧪 Antifungal Drug Development

Resistance to azole antifungals is a growing concern. Several new antifungal agents are in development:

🔸 Olorofim (F2G)

• First-in-class orotomide antifungal
• Shows activity against Aspergillus, including azole-resistant strains
• Currently in phase III trials for invasive and chronic pulmonary aspergillosis

🔸 Ibrexafungerp and Fosmanogepix

• New antifungals with different mechanisms of action
• Potentially effective in combination or for resistant cases

🔸 Inhaled Antifungals

• Trials of inhaled itraconazole, posaconazole, and PC945 (opelconazole) for direct delivery to the lungs
• Aim: higher local drug concentrations with fewer side effects

2. 🧬 Biologics and Immune Modulation

🧭 What's Next in Biologic Therapies for Severe Asthma?

Several next-generation biologics are under development, aiming to:

• Broaden coverage for patients who don't respond to existing biologics
• Target upstream pathways (beyond IL‑5, IL‑4/13, or IgE)
• Offer once-yearly dosing or dual-target activity

Examples include:

• Depemokimab: A long-acting anti-IL‑5 antibody in phase 3 trials (GSK)
• CSJ117: An inhaled anti-TSLP monoclonal antibody fragment (Novartis)
• RG6354: Targeting IL-33 pathway, an upstream trigger in type 2 and non-type 2 asthma
• Dual Biologics: Exploratory research combining two targets (e.g., IL‑5 + IL‑4 or TSLP + IL‑13)

These developments may also benefit subsets of aspergillosis patients with severe asthma or ABPA who have not fully responded to current biologics. Research is exploring biologic therapies that reduce allergic inflammation or modulate immune response, particularly for ABPA (Allergic Bronchopulmonary Aspergillosis) and overlapping asthma subtypes.

✅ Biologics Currently in Use for ABPA

Omalizumab (Xolair) – Anti-IgE

• Target: IgE antibody—blocks allergic immune response to Aspergillus antigens.
• Evidence: Studies show significant reductions in exacerbations, IgE, steroid use, and improved lung function.
• Clinical Use: Widely used off-label in ABPA patients with raised IgE and asthma features.

Mepolizumab (Nucala) – Anti–IL‑5

• Target: IL‑5 cytokine—reduces eosinophil inflammation.
• Use: Steroid-sparing and symptom control in eosinophilic ABPA.

Benralizumab (Fasenra) – Anti–IL‑5 Receptor

• Target: IL‑5Rα—causes rapid eosinophil depletion.
• Use: Clearing mucus plugs and reducing flares; often used after mepolizumab failure.

Dupilumab (Dupixent) – Anti–IL‑4Ra

• Target: IL‑4/IL‑13 pathway—type 2 inflammation.
• Use: Shown to reduce IgE levels and ABPA exacerbations.

Tezepelumab (Tezspire) – Anti‑TSLP

• Target: TSLP—broadly suppresses upstream allergic inflammation.
• Evidence: Early reports suggest benefit in ABPA patients, though data are limited.

📊 Real-World Effectiveness

UK-based retrospective study (2014–2022):

• 74 ABPA patients treated with biologics
• 65% showed ≥50% reduction in steroid use after 12 months
• 35% switched due to lack of effect or side effects

📌 Summary Table of Biologics

Biologic	Target	Use in Aspergillosis	Key Benefits
Omalizumab	IgE	ABPA with raised IgE	↓ Exacerbations, ↓ steroids, ↑ FEV₁
Mepolizumab	IL‑5	Eosinophilic ABPA	Steroid-sparing, symptom control
Benralizumab	IL‑5Rα	Refractory cases	Mucus clearance, eosinophil depletion
Dupilumab	IL‑4/IL‑13	Mixed allergic/eosinophilic ABPA	↓ IgE, ↓ flares
Tezepelumab	TSLP	Emerging, broad asthma-ABPA	Broad inflammation control

3. 🧫 Diagnostic Advances

Improved diagnostics aim to detect disease earlier and more accurately:

• Lateral flow tests (e.g., Aspergillus-specific LFD) for rapid diagnosis
• PCR testing and galactomannan assays in blood, sputum, or BAL
• Aspergillus-specific IgG and IgE testing to distinguish CPA, ABPA, and colonisation
• Next-generation sequencing (NGS) for strain typing and resistance detection

4. 🌡️ Non-Pharmacological Research

🌀 Airway Clearance and Physiotherapy

• Trials assessing flutter devices, oscillating PEP, and manual physiotherapy in chronic aspergillosis and bronchiectasis

🥦 Nutrition and Gut-Lung Health

• Increasing interest in the role of dietary fibre, gut microbiome, and short-chain fatty acids in immune defence and lung inflammation

💨 Air Quality and Exposure

• Home-based studies evaluating the impact of HEPA filters, spore counts, and environmental remediation

5. 🛡️ Preventative Strategies

🫁 Lung/Nasal Coatings (Experimental)

• Early research into coating the lungs or nasal passages to prevent infection
• Not yet in human trials for aspergillosis, but promising in animals for viral and bacterial prevention

💉 Vaccines

• No approved vaccines yet, but exploratory work is underway for high-risk populations

6. 🧫 Clinical Trials in Aspergillosis

A wide range of clinical trials are currently underway or recently completed, focusing on new antifungals, biologics, and non-pharmacological interventions:

🧪 Antifungal Trials

• Rezafungin – A long-acting echinocandin administered once weekly, currently in trials for prevention and treatment of invasive fungal infections, including those caused by Aspergillus species
• Olorofim (F2G) – Phase III trials for CPA and invasive aspergillosis
• PC945 (Opelconazole) – Inhaled triazole for CPA and prophylaxis in immunocompromised patients
• Fosmanogepix and Ibrexafungerp – Investigated in resistant and invasive fungal disease

🧬 Biologic Trials

• Tezepelumab and Dupilumab – Trials involving patients with ABPA and severe asthma
• Depemokimab (GSK) – Phase III trials for long-acting IL‑5 blockade

🌡️ Other Trials

• Airway clearance studies – Use of physiotherapy and flutter/PEP devices in chronic pulmonary aspergillosis
• Gut microbiome and fibre supplementation – Exploring anti-inflammatory potential in lung disease

These trials often recruit patients from UK centres including the National Aspergillosis Centre, and are registered on databases such as ClinicalTrials.gov.

7. 🤝 Patient Support and Outcomes Research

📊 Real-World Evidence

• Registries and observational studies (e.g., LIFE, FungiScope) gathering long-term data on patients with CPA, ABPA, SAFS, and invasive disease

👥 Quality of Life and Patient-Reported Outcomes

• Surveys and tools to measure impact of fatigue, breathlessness, mental health, and medication side effects
• Aim: improve personalised care and support services

🧭 Where to Find Updates

• ClinicalTrials.gov – searchable by "aspergillosis"
• Aspergillosis.org – for patient-friendly research summaries
• National Aspergillosis Centre (UK) – involved in many UK-based studies
• Journal of Fungi, Medical Mycology, Clinical Infectious Diseases – leading sources of peer-reviewed studies

📢 Final Word

Research into aspergillosis is accelerating across drug development, diagnostics, prevention, and patient support. While not all options are available yet, many are in trials or early clinical use. Staying informed and involved—whether through trial participation or feedback—helps shape better care for all.

Updated July 2025 – suitable for patients, clinicians, and advocacy groups.

 

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by GAtherton

🫁 Could Lung or Nasal Coatings Help Prevent Aspergillosis?

As research into new ways of preventing lung infections advances, some patients with aspergillosis are asking whether coating the lungs or airways—with a protective spray, gel, or surfactant—might one day protect them from fungal disease.

Here’s what the science says so far.

🔬 What Is Being Researched?

Scientists are currently studying ways to coat the lungs or nasal passages with a protective substance designed to:

• Trap or neutralise viruses, bacteria, or fungal spores
• Stabilise the lung or airway lining
• Prevent inflammation or infection from taking hold

These coatings may come in the form of:

• Dry powder aerosols (inhaled)
• Drug-free nasal gels or sprays

Importantly, these are being developed as preventative measures, not as treatments for people already ill.

🧪 Current Research: Early-Stage, Not Yet for Aspergillosis

1. Dry Powder Lung Surfactants

• These are based on natural surfactants that coat the lungs and keep the air sacs (alveoli) open.
• Tested in animals (e.g., lambs, rabbits) with good results in preventing respiratory distress or injury.
• Used mostly in neonatal care for premature babies.
• Not yet tested for fungal infections or chronic diseases like aspergillosis.

2. Nasal Gel-Coating Sprays

• These sprays form a temporary coating in the nose and upper airways, shown in mice to block viruses like flu or COVID-19.
• Protective effect may last several hours.
• Still in animal testing—no human trials or approvals yet.
• No evidence yet that they can prevent fungal infections like Aspergillus.

📌 Are These Coatings Available Yet?

No. As of now:

• There are no licensed lung or nasal sprays designed to prevent aspergillosis or other fungal lung infections.
• Most studies are in pre-clinical stages (animal research only).
• It may be several years before any human trials begin.

🛡️ Who Might Receive These Preventatives in the Future?

If future research proves these coatings are safe and effective, likely priority groups would include:

🎯 High-risk populations:

• People with chronic aspergillosis (CPA) or ABPA
• Patients on long-term steroids or immunosuppressants
• Individuals with bronchiectasis, COPD, or cystic fibrosis
• Transplant recipients or those with cancer or immune deficiencies
• Elderly people, especially in care homes
• Healthcare or construction workers exposed to dust, spores, or mould
• Hospitalised or ventilated patients (e.g. risk of CAPA in ICU)

❗ What Aspergillosis Patients Should Know

• These technologies are not available yet and remain in the research phase.
• They are being explored as preventative tools, not as treatment for existing fungal infections.
• There is no evidence yet they can prevent Aspergillus infections—but the research is promising.

✅ What You Can Do Now

Until better preventatives are developed, people with aspergillosis can reduce risk by:

• Avoiding high-risk environments (e.g., compost, renovation dust, decaying vegetation)
• Using prescribed antifungals or steroids correctly
• Supporting immune health (e.g., good nutrition, rest, fibre-rich diet)
• Asking doctors about biologics or ongoing research trials if relevant

📘 Final Word

While the idea of coating the lungs or nose to stop infections sounds futuristic, it’s grounded in real science. For people vulnerable to fungal lung disease, this kind of innovation may one day offer protection—especially for those on immunosuppressive treatments or with fragile lungs.

But for now, the best defence remains personalised treatment, avoidance strategies, and good communication between specialists and GPs. We’ll keep watching this space closely as research develops.

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by GAtherton