F2G announced the US Food and Drug Administration (FDA) has granted an additional Breakthrough Therapy Designation to its lead first-in-class candidate, olorofim, for the indication of “Treatment of Central Nervous System (CNS) coccidioidomycosis refractory or otherwise unable to be treated with standard of care therapy.” This is the second Breakthrough Therapy Designation for olorofim; a designation was granted previously on 11 November 2019 for “Treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory orintolerant tocurrently available therapy, and infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species.” Olorofim (formerly F901318) is the first antifungal agent to be granted Breakthrough Therapy Designation.

Olorofim has orphan drug designation in the United States for coccidioidomycosis, an endemic fungal infection with a geographic distribution focused mainly in the desert Southwest of the United States but also including Mexico, Central America, and South America. Infection begins by inhalation and can spread to any part of the body, even in otherwise healthy individuals. Spread to the brain is particularly feared as it produces a devastating illness that cannot always be controlled with any currently available agent.

Patients with coccidioidomycosis are being studied in an ongoing open-label single-arm Phase 2b study (ClinicalTrials.gov Identifier: NCT03583164) in patients with proven invasive fungal disease (IFD) or probable invasive aspergillosis (IA) and either refractory disease, resistance, or intolerance to available agents. Olorofim has been well tolerated across more than 30 years of cumulative patient dosing days with a median therapy duration of 12 weeks. Preliminary data from this study were provided to the FDA as part of the Breakthrough Therapy Designation submission.

Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition and is granted based on preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Breakthrough Therapy Designation conveys all the features of fast track designation, more intensive FDA guidance on an efficient drug development program, an organizational commitment by FDA to involve senior managers, and eligibility for rolling review and priority review.

"The granting of a second FDA Breakthrough Therapy Designation will further support our goal of rapidly developing this novel treatment for patients suffering from serious and life-threatening fungal infections. Olorofim acts via a novel and differentiated mechanism to traditional antifungals, and preliminary data have indicated that it is efficacious in tackling life-threatening invasive fungal infections that cannot be managed with currently approved agents,” Commenting on the news, Ian Nicholson, CEO of F2G Ltd, said. "Our Phase 2b programme is on track with over 85 patients recruited in Europe, Asia, and the US. We look forward to working closely with the US FDA to accelerate development of this therapy for patients having limited or no approved treatment options for an invasive mold infection."