After years of antifungal resistance increasingly making standard-of-care treatments less effective, F2G and Shionogi have released phase 3 data for the oral antifungal drug, olorofim, demonstrating its non-inferiority compared with an existing drug for invasive aspergillosis.
In a June 18 release, F2G and Shionogi shared data from the global OASIS study, which included patients with refractory infections or who were unsuitable for cornerstone azole therapy.
The data showed that the rate of all-cause mortality at day 42 was 23.8% for olorofim compared with 24.3% for AmBisome, an IV treatment option for the fungal infection. In both treatment cohorts, patients received subsequent standard care based on their condition.
The trial also revealed that drug-related treatment-emergent adverse events occurred in 35.8% of patients who received olorofim and 63.9% of those who received AmBisome. AmBisome is administered through a slow IV infusion, while olorofim is an oral medication.
Invasive aspergillosis is a life-threatening fungal infection with limited treatment options that often affects cancer and transplant patients with compromised immune systems. The most common antifungal medications are azoles, which target and inhibit an enzyme called lanosterol demethylase.
Aspergillus fumigatus, which causes aspergillosis, has become increasingly resistant to azoles over the years due to their agricultural use, which has enabled mutations to develop. Olorofim belongs to a new class of antifungals and inhibits dihydroorotate dehydrogenase, disrupting the synthesis of pyrimidines, which are essential to fungal growth.
There has not been a novel mechanism for the treatment of invasive aspergillosis in more than 20 years. In an interview, F2G Chief Medical Officer John Rex, M.D., said he is bullish on the potential impact of olorofim. “It’s a brand-new class, it’s oral, it works for resistant aspergillosis, and it works for infection-resistant strains,” he told Fierce Biotech. “You can do an IV for a long time if you have to, but it’s got its own burdens, and the pill opens up doors.”
The recent data follow a winding path for olorofim, which received a Breakthrough Therapy Designation from the FDA in 2019. Shinogi teamed up with F2G in 2022 via a $100 million upfront payment for the Asian and European rights to olorofim. But in 2023, F2G received a complete response letter from the FDA after the regulator requested additional data and analyses following the biotech’s phase 2b study in various invasive fungal infections.
The setback sent F2G back to the boardroom, but the U.K. biotech was still able to raise $100 million in 2024 to complete the late-stage development of olorofim and support potential commercialization. The phase 3 data represent another step in that process.
“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,” Johan Maertens, M.D., Ph.D., professor of hematology at University Hospitals in Leuven, Belgium, and the study’s principal investigator, said in a statement. “We’re hopeful this could offer a meaningful alternative for clinicians to treat challenging infections caused by aspergillus.”
F2G and Shionogi plan to present the results at a future medical conference and will follow with regulatory submissions in the U.S. by F2G and in Europe and Asia by Shionogi.
F2G’s execs are encouraged by the prospects of a novel mechanism capable of treating resistant strains of aspergillus while offering a more convenient mode of delivery.
“These findings demonstrate the potential for olorofim to serve as a new option for patients with difficult-to-treat invasive fungal infections, including invasive aspergillosis,” Francesco Maria Lavino, F2G CEO, said in the release.