F2G and Shionogi have reported that oral olorofim met the primary endpoint of non-inferiority versus AmBisome followed by standard of care in patients with invasive aspergillosis who were refractory to or unsuitable for azole therapy.

All-cause mortality at day 42 was broadly comparable between the two arms, at 23.8% for olorofim and 24.3% for AmBisome followed by standard of care, a difference of -0.5% with overlapping confidence intervals. Safety data also showed fewer drug-related treatment-emergent adverse events in the olorofim arm, at 35.8% compared with 63.9% in the comparator arm, driven largely by renal events in the AmBisome group.

The companies said no new safety signals were identified. The study enrolled 225 patients in a 2:1 randomised design and represents a key dataset for a patient group with limited treatment options and rising antifungal resistance concerns.

Invasive aspergillosis remains a severe, often life-threatening fungal infection, particularly in immunocompromised patients, and current treatment options can be limited by toxicity and resistance issues.

Professor Johan Maertens, principal investigator of the study, highlighted the unmet need in this population, saying: “Invasive fungal infections remain difficult to treat and can be life-threatening especially in immunocompromised patients,” said Maertens: “The OASIS topline results add to the growing body of evidence supporting olorofim’s therapeutic potential in a hard-to-treat population with limited antifungal options. We’re hopeful this could offer a meaningful alternative for clinicians to treat challenging infections caused by Aspergillus.”

F2G chief executive Francesco Maria Lavino said the outcome marks an important step for the programme and the company’s collaboration with Shionogi, noting that the data support olorofim as a potential new option for difficult-to-treat invasive fungal infections.

Shionogi senior vice president R&D Dr John Keller said safety and tolerability remain key challenges in antifungal treatment, particularly with existing agents that can affect renal function, and that the results suggest olorofim could offer a differentiated profile if approved.

Olorofim is a first-in-class orotomide antifungal with a novel mechanism of action and oral dosing, targeting Aspergillus species including strains resistant to existing therapies. If approved, it would represent the first new mechanism antifungal option for invasive aspergillosis in more than 20 years.

Regulatory submissions are planned in the US by F2G and in Europe and Asia by Shionogi, with full data to be presented at a future medical congress.

The data position olorofim as a potential new oral treatment option in a setting where clinicians currently rely on limited antifungal classes, often constrained by toxicity, resistance, and route of administration challenges.