Hope on the horizon: Novel antifungal treatments in development

For many people with aspergillosis, today’s antifungal medicines make a real difference. They can control infection, improve symptoms and help prevent further lung damage. However, treatment can also be difficult: medicines may cause side effects, interact with other drugs, be hard to absorb consistently, or become less effective if the fungus is resistant.

That is why researchers are developing new antifungal treatments. This is encouraging progress, but it is important to be clear about what it means: a medicine in development is not yet a treatment option for most people. It must first be tested carefully for safety, the right dose and whether it works better than, or alongside, existing treatment.

Why are new antifungals needed?

Aspergillosis is not one single illness. It includes allergic conditions such as ABPA, chronic pulmonary aspergillosis (CPA), aspergilloma and severe invasive infection. The right treatment depends on the type of aspergillosis, how active it is, a person’s underlying lung health and immune system, and the results of scans, blood tests and microbiology.

The azole antifungals—such as itraconazole, voriconazole, posaconazole and isavuconazole—are important treatments. They have helped many people live with and manage aspergillosis. Yet they can be challenging because:

• levels of some medicines vary between people, so blood-level monitoring may be needed;
• they can interact with other prescribed medicines, over-the-counter remedies and supplements;
• some people experience troublesome side effects or changes in liver blood tests;
• Aspergillus can sometimes be resistant to azole treatment;
• some people have complex illness that needs a different approach, combination treatment or specialist advice.

New treatments are being designed to work in different ways from older medicines. In time, this may provide alternatives for people who cannot tolerate an existing medicine, whose infection is resistant, or whose illness has not responded as hoped.

What is being developed?

There are several investigational antifungal medicines and approaches in development. Not all will become licensed treatments, and not every medicine being studied is aimed specifically at every form of aspergillosis.

Medicines with new targets

Most established antifungals work by disrupting parts of the fungal cell membrane or cell wall. Several newer medicines aim at different fungal processes. This matters because a different target may mean a medicine can still work when resistance or intolerance limits another option.

Olorofim is one example of a newer oral antifungal that has been studied for difficult-to-treat invasive fungal infections, including infections caused by Aspergillus. It works differently from azole medicines. Research has particularly focused on situations where established treatment is unsuitable or has not worked.

Fosmanogepix is another investigational antifungal with a different mechanism of action. It has been studied in serious invasive fungal infections and has attracted interest because of its activity against a range of fungi. Its eventual role, if licensed, will depend on the results of clinical studies and decisions by medicines regulators.

Weekly intravenous treatment: rezafungin

Rezafungin is a newer echinocandin antifungal given by intravenous infusion, usually once a week. Echinocandins work differently from azole medicines: they interfere with the fungal cell wall. Rezafungin is already used for some serious fungal infections, but its role in aspergillosis is still being researched.

A clinical study is assessing whether six months of rezafungin treatment can be helpful and safe for people with chronic pulmonary aspergillosis (CPA) who have limited treatment options. A once-weekly treatment could be particularly useful for some people who cannot take, absorb or tolerate long-term oral azoles. However, it remains a clinical-trial treatment for CPA rather than standard care.

Getting treatment directly to the lungs

Researchers are also exploring whether antifungal medicines can be delivered directly to the lungs by inhalation. Pulmazole, an inhaled formulation of itraconazole, was developed with this aim: high levels of medicine at the site of infection, with less medicine circulating around the rest of the body.

This approach is appealing, particularly for long-term lung conditions, but inhaled antifungal treatment is not currently routine care for aspergillosis. Pulmazole is best understood as an example of an important research direction rather than an available treatment. Other inhaled antifungal formulations have also been investigated.

Other medicines and treatment strategies are also being explored. These include new formulations, possible combination approaches and treatments designed to address resistant fungi. Research is active, but progress is rarely straightforward: studies may change, take longer than expected or show that a medicine is useful only for a particular group of patients.

What does “in development” actually mean?

Before a medicine can be routinely prescribed, it usually passes through several stages of research. Early studies look at safety and how the body handles the medicine. Later studies assess dose, side effects and whether it works in people with the infection it is intended to treat.

Even when early results are promising, researchers still need to establish important questions:

• Who is most likely to benefit?
• What dose is safest and most effective?
• How does it compare with current treatment?
• Does it work against resistant infection?
• What side effects, interactions and monitoring are needed?
• Can it be used safely with other treatments people may need?

Only after sufficient evidence has been reviewed can a regulator decide whether to license a medicine for a particular use. A medicine may be available in one country but not another, or only for a specific type of infection.

Clinical trials: a route to better treatment

Clinical trials are how new treatments become available. People who take part contribute to better care for future patients, and some may gain access to a treatment not otherwise available. However, a trial is not simply a way to obtain a new medicine.

Every study has strict eligibility criteria. These may relate to the type of aspergillosis, scan findings, fungal culture results, previous antifungal treatment, other medicines, liver or kidney function, and whether someone has another health condition. Some trials compare a new medicine with usual care; others do not provide the study medicine to every participant.

If you hear about a trial and wonder whether it may be relevant, ask your treating respiratory, infectious diseases or aspergillosis specialist. They can advise whether it is appropriate and, if needed, seek specialist or trial-centre advice. It is completely reasonable to ask—but it is equally reasonable for the answer to be that current treatment remains the better option for you.

What about off-label or unlicensed treatment?

Sometimes a specialist may consider an antifungal medicine outside its usual licence. This may be described as off-label use: the medicine is licensed, but not specifically for your type of aspergillosis, dose or treatment situation. This is not unusual in complex or rare diseases, but it requires careful specialist judgement, discussion of the uncertainty, and appropriate monitoring.

In exceptional circumstances, an investigational medicine may also be available through a clinical trial, a named-patient arrangement or an early-access programme. These routes are tightly controlled and are not a guarantee of treatment. They are usually considered only when standard options have been unsuitable, ineffective or cannot be used safely.

Whether any of these options is appropriate depends on your diagnosis, previous treatment, fungal test results, other health conditions and the potential balance of benefit and risk. Your specialist team can advise whether there is a realistic route worth exploring.

What this means for you now

News about new antifungal medicines can bring hope, particularly if you have had a difficult experience with treatment. It can also create uncertainty or make you question a medicine you are taking now. The most important point is that treatment decisions should be based on your current health, diagnosis and test results, not on headlines about a treatment that may still be years away from routine use.

If your current antifungal is helping, monitoring and review are part of making that treatment as safe and effective as possible. If you are struggling with side effects, taking other medicines, finding doses difficult, or worrying that treatment is not working, tell your team. There may be practical solutions, such as checking drug levels, reviewing interactions, changing the timing or formulation of a medicine, managing side effects, or considering an alternative treatment.

Do not feel that you have to “put up with” problems in silence. Equally, do not stop an antifungal suddenly unless a clinician has advised you to do so. A supported discussion with your specialist team is the best way to balance the benefits and risks of treatment.

Questions you may want to ask at an appointment

• What is the aim of my antifungal treatment at the moment?
• How will we know whether it is working?
• Do I need blood tests or antifungal drug-level monitoring?
• Could any of my other medicines, vitamins or supplements interact with it?
• What symptoms or side effects should I report promptly?
• Is there a different treatment approach if this medicine is not suitable for me?
• Are there any relevant clinical trials now or likely in the future?

Keeping hope realistic

There is genuine momentum in antifungal research. New medicines, better diagnostics and greater awareness of fungal disease all have the potential to improve care. But good care today still depends on timely diagnosis, expert interpretation of tests, careful monitoring and shared decisions between patients and their clinical teams.

The future is promising—not because every new medicine will be right for every person, but because more research should mean more informed choices when people need them.

This page is for general information and does not replace personalised medical advice. If you have concerns about your antifungal treatment, contact your prescribing clinical team or specialist.

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