Announcement • Jun 18
F2G Ltd and Shionogi Announces Positive Topline Results from Global Phase 3 Oasis Study Evaluating Oral Olorofim Versus Ambisome Followed by Standard of Care in Patients with Invasive Aspergillosis F2G Ltd. and Shionogi & Co., Ltd. announced positive topline results from the global Phase 3 OASIS study (NCT05101187), comparing the investigational oral antifungal drug olorofim versus AmBisome (liposomal amphotericin B for injection) followed by standard of care in patients with invasive aspergillosis whose infection is either refractory to or unsuitable for azole therapy. The study met its primary endpoint of non-inferiority, with a rate of all-cause mortality (ACM) at Day 42 for olorofim of 23.8% vs. 24.3% for AmBisome followed by standard of care (difference of -0.5% with 95% confidence interval of -13.1 to 10.8%). No new safety findings were observed for olorofim; the rate of drug-related treatment-emergent adverse events (TEAEs) was 35.8% for olorofim and 63.9% for AmBisome followed by standard of care, with the difference mainly driven by the higher rate of renal events in the AmBisome arm. These results expand on the previous Phase 2b study data that led to olorofim’s Breakthrough Therapy Designations from the U.S. Food and Drug Administration (FDA), reinforcing olorofim’s potential as a treatment for patients with invasive aspergillosis. F2G and Shionogi plan to present pivotal results from the study at a future medical congress. These data will be submitted to regulatory authorities in the U.S. by F2G and in Europe and Asia by Shionogi. Invasive aspergillosis is a life-threatening fungal infection that primarily affects immunocompromised patients and is associated with substantial morbidity and mortality. Treatment options are limited for patients who cannot be treated with available azole antifungal therapies. F2G and Shionogi are collaborating to develop and commercialize olorofim and bring this novel antifungal therapy to patients with invasive fungal infections. F2G has commercial responsibility for olorofim in North America and non-Shionogi territories, and Shionogi has commercial responsibility for olorofim in Europe and Asia. The Phase 3 OASIS (Olorofim Aspergillus Infection Study) trial (NCT05101187) was a global, randomized study that evaluated the efficacy and safety of olorofim versus AmBisome followed by standard of care in adult patients with invasive aspergillosis whose infection is either refractory to or unsuitable for azole therapy. OASIS was designed as a non-inferiority study using a non-inferiority margin of 20% comparing outcomes in 225 subjects randomized 2:1 to olorofim or AmBisome-based standard of care. Invasive aspergillosis is a life-threatening fungal infection with limited treatment options due to rising drug resistance and toxicity concerns. The study’s primary endpoint was all-cause mortality at Day 42, with additional measures of clinical response, safety, and quality of life. Olorofim (formerly, F901318) is F2G's leading candidate from the orotomide class and has been studied in a recently completed global Phase 3 trial ("OASIS", NCT05101187). Olorofim is a first-in-class antifungal with a novel mechanism of action, oral dosing, and activity against a wide range of Aspergillus species, including strains that are resistant to currently approved agents. If approved based on the Phase 3 OASIS data, olorofim will be the first novel mechanism agent for invasive aspergillosis in more than 20 years. In the U.S., olorofim has received orphan drug status from the FDA for the treatment of invasive aspergillosis, scedosporiosis, invasive scopulariopsis, and coccidioidomycosis. Olorofim has been granted Qualified Infectious Disease Product (QIDP) designation for several invasive fungal infections, including invasive aspergillosis and coccidioidomycosis. Additionally, olorofim has also received two Breakthrough Therapy designations (BTD) from the FDA. The first BTD was for the treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory or intolerant to currently available therapy, and infections due to Lomentospora prolificans, Scedosporium and Scopulariopsis species. The second BTD was for the treatment of central nervous system (CNS) coccidioidomycosis refractory or otherwise unable to be treated with standard of care therapy. In Europe, olorofim has been granted orphan designation from the European Medicines Agency for the treatment of invasive aspergillosis, scedosporiosis, and invasive scopulariopsis. Olorofim is an investigational therapy and has not been approved by any regulatory authorities. 
