Lancet Infect Dis

Investigational agent offers hope for invasive fungal infections with limited treatment options

June 24, 2025

Study details: This single-arm, open-label, phase 2b study evaluated olorofim in 203 patients with proven or probable invasive fungal disease (IFD) who'd exhausted standard antifungal options. Conducted between 2018 and 2022, the trial included patients infected with Aspergillus spp. (n=101, including 22 azole-resistant), Lomentospora prolificans (n=26), Scedosporium spp. (n=22), Coccidioides spp. (n=41), and other rare fungi.

Results: At day 84, 27% of patients achieved a successful global response (95% confidence interval [CI], 21–34), while 63% showed stable disease or better (95% CI, 56-70). Clinical response was observed in 54% of patients. All-cause mortality was 12% at day 42 and 16% at day 84. The median treatment duration was 84 days, with some patients receiving extended therapy for up to 988 days. Liver enzyme elevations occurred in 10% of patients, and were managed by dose adjustment or discontinuation. GI intolerance was also reported in 10%, mostly mild and self-limiting. No treatment-related deaths occurred.

Clinical impact: Olorofim demonstrated meaningful clinical activity and a manageable safety profile in patients with difficult-to-treat IFDs. Its novel mechanism and oral formulation make it a promising candidate for addressing antifungal resistance and rare mold infections.

Source:

Maertens JA, et al. (2025, June 17). Lancet Infect Dis. Olorofim for the treatment of invasive fungal diseases in patients with few or no therapeutic options: a single-arm, open-label, phase 2b study. https://pubmed.ncbi.nlm.nih.gov/40541222/