F2G olorofim matches AmBisome in Phase 3 invasive aspergillosis trial
F2G and Shionogi have reported topline results from the global Phase 3 OASIS trial evaluating oral olorofim against intravenous liposomal amphotericin B (AmBisome) followed by standard of care in adult patients with invasive aspergillosis who could not receive azole therapy. The data were presented in a late-breaking oral session at IDWeek 2026 on 22 October.
The trial randomised 225 patients 2:1 to olorofim or AmBisome-based standard of care. It met its primary endpoint: all-cause mortality at Day 42 was 23.8% in the olorofim arm versus 24.3% in the comparator arm, a difference of -0.5 percentage points (95% CI: -13.1 to 10.8%), comfortably within the pre-specified 20% non-inferiority margin agreed with both the FDA and the EMA's Committee for Medicinal Products for Human Use.
Efficacy and safety
Secondary efficacy endpoints tracked closely between arms. The independent Data Review Committee-assessed global response rate at Day 42 was 26.5% for olorofim versus 31.1% for AmBisome-based care; by Day 84 the figures had converged at 30.5% versus 28.4%. All-cause mortality at Day 84 stood at 32.5% versus 29.7%, a non-significant difference. The enrolled population was severely immunocompromised: approximately 79% had haematologic malignancies or had undergone stem cell transplantation, and around 40% were neutropenic at enrolment.
The safety comparison strongly favoured olorofim. Drug-related adverse events occurred in 35.8% of olorofim-treated patients versus 63.9% of those receiving AmBisome-based care; serious drug-related adverse events were reported in 4.0% and 18.1% respectively. The gap was driven largely by renal toxicity, a well-documented liability of amphotericin B formulations: drug-related renal adverse events arose in just 1.3% of the olorofim arm compared with 22.2% in the comparator arm. Drug-induced liver injury, an acknowledged signal for olorofim seen in earlier studies, occurred at similar rates in both arms at around 4.5%. Patients on olorofim were also discharged from hospital earlier, after an average of 17 days versus 28 days in the comparator group.
Johan Maertens, Professor of Haematology at University Hospitals Leuven and the study's principal investigator, said: "Having an oral option like olorofim, with data supporting its safety in challenging patients, including those with complex drug interactions, would give me another valuable tool in the fight against this fungal infection."
Regulatory path and market context
F2G plans to resubmit a New Drug Application to the FDA before the end of 2026, building on a previous submission. Shionogi will file in Europe and Asia. If approved, olorofim would be the first antifungal with a novel mechanism of action for invasive aspergillosis to reach the market in more than 20 years. The drug targets dihydroorotate dehydrogenase in the pyrimidine biosynthesis pathway, a mechanism entirely distinct from the azoles, polyenes and echinocandins that currently define standard care.
The antifungal pipeline has historically attracted limited investment relative to antibacterials, leaving patients with azole-resistant or azole-intolerant aspergillosis with few oral options. Rising rates of azole resistance in Aspergillus fumigatus, documented across Europe and Asia, have sharpened clinical interest in agents with alternative mechanisms. Olorofim already holds two FDA Breakthrough Therapy designations, orphan drug status in the US, and orphan designation from the European Commission, regulatory signals that reflect the unmet need. The combination of oral dosing, a clean renal profile and activity against resistant strains positions it as a meaningful addition to a thin formulary, provided the FDA accepts the resubmission and does not request additional data on the liver-injury signal.