F2G and Shionogi have reported positive Phase III results for the antifungal drug olorofim in patients with invasive aspergillosis who are not eligible for standard azole therapy. If approved based on this data, olorofim would become the first antifungal agent with a novel mechanism of action for invasive aspergillosis in over two decades.
“Invasive fungal infections remain difficult to treat and can be life-threatening especially in immunocompromised patients,” said Johan Maertens, MD, PhD, professor of hematology at University Hospitals Leuven in Belgium and principal investigator of the study. “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.”
Invasive aspergillosis is a fungal infection with high mortality rates that mainly affects immunocompromised patients. Due to rising drug resistance and toxicity profiles of currently available therapies, a growing number of patients cannot be treated with azole antifungals, leaving them with limited options.
Olorofim belongs to a new class of antifungal agents called orotomides that was discovered by F2G. These drugs can selectively target an enzyme essential for the synthesis of pyrimidine that is shared across mold fungi including Aspergillus, making olorofim effective against a broad range of species including rare and drug-resistant strains.
The Phase III OASIS study recruited 225 adults with invasive aspergillosis who either had a refractory infection or were unsuitable for azole therapy. Participants received either oral olorofim or amphotericin B—an antifungal used to treat serious infections known for causing kidney toxicity.
After 42 days, the mortality rate among patients who took olorofim was 23.8%, compared to 24.3% for the control group. The rate of adverse events caused by the treatment was 35.8% for olorofim versus 63.9% for amphotericin B, with the difference being mostly driven by a higher rate of kidney toxicity in the control group.
“This is a promising new development in antifungal medicine—an area where patients have been underserved for more than 20 years,” said John Keller, PhD, director of the board and senior vice president of R&D at Shionogi. “In current clinical practice, safety and tolerability considerations, particularly effects on renal function, can pose significant challenges for treatment selection and continuation. Against this background, the results of the OASIS study suggest that olorofim has the potential to offer a new treatment option for patients with invasive aspergillosis.”
Based on these results, Shionogi and F2G plan to submit approval applications with regulatory authorities across the world. Under their commercial agreement, Shionogi will be responsible for commercialization in Europe and Asia, while F2G will oversee North America and other remaining territories.
Over the past 20 years, most newly approved antifungal drugs have belonged to existing drug classes, limiting progress against the growing threat of antimicrobial resistance. During that period, only a single antifungal with a novel mechanism of action reached the market: ibrexafungerp, which is approved for the treatment of vulvovaginal candidiasis infections. If approved, olorofim would offer a much-needed option in an indication where both existing treatment choices and therapeutic innovation have historically remained limited.
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