Phase 3 OASIS trial shows Shionogi and F2G’s investigational antifungal olorofim achieved non-inferior survival to AmBisome in invasive aspergillosis, with fewer renal toxicities. Regulatory filings planned in U.S., Europe, and Asia.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Shionogi and F2G have reported positive topline results from the global Phase 3 OASIS trial evaluating the investigational antifungal olorofim in patients with invasive aspergillosis whose infections were either refractory to or unsuitable for azole therapy.
The study achieved its primary endpoint of non-inferiority for all-cause mortality at Day 42. Mortality rates were 23.8% in the olorofim arm and 24.3% in patients treated with liposomal amphotericin B (AmBisome®) followed by standard of care, resulting in a treatment difference of -0.5%.
No new safety signals emerged during the study. Drug-related treatment-emergent adverse events occurred in 35.8% of patients receiving olorofim compared with 63.9% of those receiving AmBisome-based therapy, largely due to a higher incidence of renal adverse events in the comparator arm.
Addressing a Long-Standing Need in Antifungal Therapy
Invasive aspergillosis is a severe and often fatal fungal infection that primarily affects immunocompromised individuals, including patients with hematologic malignancies, organ transplants, and prolonged immunosuppression. Mortality remains high despite available treatments, and therapeutic options become particularly limited when azole antifungals fail or cannot be used.
Olorofim belongs to the novel orotomide class of antifungals and works by inhibiting fungal dihydroorotate dehydrogenase, an enzyme essential for pyrimidine biosynthesis. This mechanism differs from currently approved antifungal classes and may offer activity against Aspergillus strains resistant to existing therapies.
If approved, olorofim would become the first antifungal agent with a new mechanism of action for invasive aspergillosis in more than 20 years.
Phase 3 OASIS Trial Details
The randomized global OASIS study (NCT05101187) enrolled 225 adults with invasive aspergillosis and assigned participants in a 2:1 ratio to receive either oral olorofim or AmBisome followed by standard care.
The trial used a non-inferiority design with a predefined margin of 20%. In addition to all-cause mortality at Day 42, investigators evaluated clinical response, safety outcomes, and quality-of-life measures.
The results build on earlier Phase 2b findings that supported two FDA Breakthrough Therapy Designations for olorofim. The drug has also received Orphan Drug and Qualified Infectious Disease Product (QIDP) designations in the United States for multiple invasive fungal infections.
Investigators Highlight Potential Clinical Impact
Principal Investigator Johan Maertens, MD, PhD, of University Hospitals Leuven, noted that invasive fungal infections remain difficult to treat and often carry a high mortality risk in immunocompromised patients. He said the OASIS findings strengthen the growing evidence supporting olorofim as a potential treatment option for patients with limited antifungal choices.
Shionogi’s R&D leadership emphasized that the lower rate of treatment-related adverse events, particularly renal complications, could represent an important advantage in clinical practice where toxicity frequently influences treatment decisions.
F2G CEO Francesco Maria Lavino described the study as a major milestone for both companies and highlighted olorofim’s potential role in addressing difficult-to-treat invasive fungal infections.
Regulatory Path Forward
The companies plan to present detailed OASIS data at an upcoming medical congress and submit the findings to regulatory authorities. F2G will lead regulatory filings in the United States, while Shionogi will oversee submissions across Europe and Asia.
If approved, olorofim could expand treatment options for patients with invasive aspergillosis who have limited alternatives and help address a significant unmet need in antifungal medicine.
What This Means for Patients
Patients with invasive aspergillosis who cannot receive azole antifungal therapy often face limited treatment options and significant treatment-related toxicities. The Phase 3 OASIS results suggest that oral olorofim may offer survival outcomes comparable to current standard therapy while causing fewer treatment-related side effects, particularly kidney-related complications. If approved, it could provide a valuable new option for patients with difficult-to-treat fungal infections and reduce reliance on older, more toxic antifungal therapies.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.