At the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global 2026 conference in Munich, Germany, data on F2G’s first-in-class, investigational antifungal agent, olorofim, was presented.
Olorofim is an oral orotomide, which is a novel class of antifungal agents that target and inhibit dihydroorotate dehydrogenase (DHODH). It is active against resistant Aspergillus species, resistant molds, and dimorphic fungi. Olorofim has been granted orphan drug designation from both the US Food and Drug Administration (FDA) and European Medicines Association (EMA), as well as qualified infectious disease product (QIDP) designation, breakthrough therapy designation, and priority review designation from the FDA, for numerous fungal species.
Go deeper with GlobalData
Access deeper industry intelligence
Experience unmatched clarity with a single platform that combines unique data, AI, and human expertise.
The FDA previously issued a complete response letter regarding a new drug application (NDA) for olorofim in June 2023, stating that it was not able to approve olorofim at the time and requested additional data and analyses. F2G is expected to submit a revised NDA for olorofim to the FDA, although the exact timeline for this remains uncertain.
Invasive aspergillosis (IA) is a severe fungal infection, which primarily affects immunocompromised patients. Symptoms of IA can vary, depending on the organs infected, but typically include fever, chest pain, cough, coughing up blood, and shortness of breath. IA has a high mortality rate, particularly among patients with hematologic malignancies. In particular, patients infected with IA with hematologic malignancies have a 40–50% mortality rate at 12 weeks. Currently available antifungals have limitations including toxicity, drug-drug interactions, and increasing rates of resistance. Olorofim has the potential to be particularly beneficial to patients with hematologic malignancies infected with IA, as it can be administered simultaneously with immunosuppressants.
The data presented on behalf of F2G at ESCMID Global 2026 was a sub-analysis of the Phase IIb trial which investigated olorofim in individuals 16 years of age and older, presenting with invasive fungal infections caused by Aspergillus, Lomentospora prolificans, Scedosporium, Coccidioides, as well as other invasive fungi, and limited treatment options. The sub-analysis evaluated patients 16 years of age and older who were highly immunosuppressed due to hematologic malignancies, such as acute myelogenous leukemia, hematopoietic cell transplantation, and graft-versus-host disease, and presented with IA. Patients were segmented into two groups: one group included patients with hematologic malignancies without neutropenia (HM) and the other group included patients with hematologic malignancies with neutropenia at baseline (NAB).
The study investigators defined success as complete or partial response to olorofim, and global success rates at Day 42 were 34% for the HM group and 32% for the NAB group. At Day 84 these rates increased to 34% and 36%, respectively. These rates were found to be consistent with the global success rates observed in the Phase IIb study of IA patients. All-cause mortality rates at Day 42 were 27% for the HM group and 36% for the NAB group. At Day 84 these rates increased to 35% and 45%, respectively. These rates were found to be higher than the rates observed in the Phase IIb study of IA patients, but this may be attributed to the severity of the underlying disease. The safety profile of olorofim was analysed in the Phase IIb study and was found to be well-tolerated with low discontinuation rates.
Olorofim has recently completed a Phase III trial, comparing the efficacy, safety, and tolerability of the novel antifungal to AmBisome (liposomal amphotericin B) in patients with IA and limited treatment options. If successful, the entrance of olorofim into the antifungal market has a diverse potential of applications across a wide range of fungal infections, particularly for patients with hematologic malignancies and IA, for which a lack of treatment options exists.
