A once-weekly intravenous antifungal called rezafungin is being investigated as a possible treatment for chronic pulmonary aspergillosis (CPA). It could eventually provide another option for people who cannot take azole antifungals or whose infection has become resistant to them.
Early evidence includes encouraging results from one patient with difficult-to-treat CPA, together with laboratory evidence that rezafungin is active against a large collection of Aspergillus isolates. However, the main clinical trial is still underway and has not yet reported its results.
Why are new treatments for CPA needed?
CPA is usually treated with azole antifungal medicines such as itraconazole, voriconazole, posaconazole or isavuconazole. These are taken by mouth and can be effective, but treatment commonly lasts for many months and sometimes considerably longer.
Unfortunately, azoles are not suitable for everyone. Problems can include:
- side effects;
- interactions with other medicines;
- difficulty achieving an effective drug concentration;
- liver toxicity or other complications;
- the development of azole-resistant Aspergillus.
When azoles cannot be used, the alternatives are limited. Intravenous antifungals such as liposomal amphotericin B, micafungin and caspofungin may be considered, but some require daily administration and can be difficult to sustain over an extended period.
Rezafungin may offer a more convenient alternative because it only needs to be administered once a week.
What is rezafungin?
Rezafungin is a long-acting member of the echinocandin class of antifungal medicines. Echinocandins interfere with the production of beta-1,3-D-glucan, an important component of the fungal cell wall.
Rezafungin remains in the body for much longer than older echinocandins. After an initial loading dose, it can be given by intravenous infusion once weekly.
The medicine is already approved for treating invasive candidiasis, a serious infection caused by Candida. It is not currently approved as a standard treatment for CPA, and its effectiveness against CPA has not yet been established.
Encouraging experience in one patient
A case report published in JAC-Antimicrobial Resistance described the use of rezafungin in a patient with CPA and very limited treatment options.
The patient had been diagnosed with CPA in 2020 and experienced breathlessness, coughing, lethargy and repeated episodes of coughing up blood. CT scans showed progressive cavities and nodules affecting both lungs.
The patient received once-weekly intravenous rezafungin for 12 weeks through an outpatient intravenous treatment service.
During treatment:
- symptoms improved substantially;
- there were no further emergency visits, compared with eight during the preceding year;
- the patient’s Aspergillus IgG level fell from 165 to 98 mgA/L;
- CT imaging showed a slight improvement in the inflammation surrounding the lung cavities.
The treatment was also considered more convenient than an echinocandin requiring daily intravenous administration.
These findings are encouraging, but this was only one patient. A case report cannot tell us how frequently people with CPA will benefit, how long any improvement will last or how rezafungin compares with existing treatments.
The Phase 2 clinical trial
A Phase 2 study is now formally evaluating rezafungin in adults with CPA who have limited treatment options.
The international study, identified as NCT06794554, plans to include approximately 60 participants. Everyone enrolled receives rezafungin, so this is an open-label, single-arm trial rather than a comparison between rezafungin and another antifungal.
Participants receive:
- a 400 mg intravenous loading dose;
- 200 mg intravenously once a week afterwards;
- a total of 26 doses over six months.
Researchers are assessing changes in symptoms and quality of life using the St George’s Respiratory Questionnaire, together with changes in body weight and CT imaging. Safety and side effects are also being monitored.
The trial began in 2025 and is currently listed as active but no longer recruiting. No results have yet been published or posted on the trial registry. Because each participant receives six months of treatment and requires follow-up, a full analysis is unlikely to be available until 2027.
What do the laboratory findings show?
Additional laboratory results were presented at ESCMID Global in April 2026.
Researchers examined rezafungin against almost 1,000 Aspergillus isolates collected internationally over 11 years. Most were Aspergillus fumigatus, the species most commonly associated with CPA.
Rezafungin showed activity against the isolates at low laboratory concentrations, with broadly consistent results across different geographical regions. Its activity was similar to that of the existing echinocandin anidulafungin.
This supports the biological rationale for studying rezafungin in aspergillosis. However, laboratory susceptibility does not necessarily mean that a medicine will produce a meaningful improvement in patients. That is what the Phase 2 trial must establish.
Why could once-weekly treatment matter?
A treatment requiring one infusion each week could be considerably easier for patients and healthcare services than daily intravenous therapy.
Potential benefits could include:
- fewer hospital or outpatient visits;
- less disruption to patients and carers;
- easier delivery through outpatient intravenous therapy services;
- a non-azole option with fewer drug interactions;
- an additional treatment possibility for azole-resistant CPA.
Rezafungin is still an intravenous treatment, however. It would not offer the convenience of taking tablets at home, and the practicalities and cost of prolonged intravenous treatment would still need consideration.
What don’t we know yet?
Several important questions remain unanswered:
- How many people with CPA respond to rezafungin?
- How substantial are improvements in symptoms and CT appearances?
- Does it stop CPA from progressing?
- How durable is the response after treatment finishes?
- Which patients are most likely to benefit?
- Is six months the most appropriate treatment duration?
- How safe is repeated long-term treatment?
- How does it compare with azoles, other echinocandins or liposomal amphotericin B?
The present trial has no control group and is relatively small, so further comparative studies may be needed even if its results are encouraging.
A promising development—but not yet a proven CPA treatment
Rezafungin is particularly interesting because it combines a different class of antifungal activity with practical once-weekly administration. The published case demonstrates that prolonged outpatient treatment is possible and may benefit an individual with difficult-to-treat CPA. Laboratory findings also confirm activity against a large and geographically diverse collection of Aspergillus isolates.
Nevertheless, rezafungin has not yet been proven effective for CPA. The results of the Phase 2 trial will provide the first structured evidence showing how patients respond over six months.
For now, rezafungin should be viewed as a promising experimental option for people with CPA who have limited alternatives, rather than an established replacement for azole treatment.
for people with CPA who have limited alternatives, rather than an established replacement for azole treatment.
Further information
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- Rezafungin Phase 2 CPA trial – ClinicalTrials.gov
- Successful outpatient treatment with rezafungin for CPA – JAC-Antimicrobial Resistance
- Activity of rezafungin against Aspergillus species – ESCMID Global 2026 poster
- Olorofim: another antifungal being investigated for difficult-to-treat aspergillosis
