The Fungal Threat: The Uphill Battle in Developing Antifungal Drugs
In the perpetual race against evolving fungal infections, the pharmaceutical industry faces unprecedented challenges in creating effective antifungal drugs. Last summer, the Food and Drug Administration (FDA) dealt a setback to the development of a groundbreaking antifungal drug named olorofim, requesting additional data from the company. This denial marked a crucial moment, as the FDA hasn’t approved a novel antifungal drug since the early 2000s.
Amid the urgency to combat fungal infections, the World Health Organization (WHO) identified 19 priority pathogens, including the drug-resistant Candida auris and the potentially spreading coccidioides causing Valley fever. The global health threat posed by fungi is underscored by a tripling of Candida auris infections in the U.S. in 2021 alone, according to the Centers for Disease Control and Prevention.
However, the complexity of the situation extends beyond human health, intertwining with the global food system. Fungal diseases ravage crops, with up to 25% lost before harvest and an additional 20% succumbing to post-harvest fungal attacks. Farmers combat these agricultural threats with fungicides, but a concerning consequence arises – these same fungicides can render critical antifungal drugs ineffective.
Scientists have identified links between commonly used fungicides and the emergence of drug-resistant infections, exemplified by the fungus Aspergillus fumigatus in 40 countries, including the U.S. The dilemma arises from shared molecular targets between fungicides and antifungal drugs, creating a scenario where fungal resistance to fungicides translates to resistance against life-saving antifungal medications.
The urgency for new antifungals is evident, considering humans share nearly half of their DNA with fungi. Yet, finding suitable molecular targets that distinguish between fungal and human cells proves challenging, leading to antifungals with serious side effects. Moreover, fungi’s rapid ability to develop resistance further complicates the limited arsenal of antifungal drugs.
The development timeline for new antifungal drugs is lengthy – about 25 years – and a similar timeline applies to fungicides. Identifying viable molecular targets in fungal cells has proven challenging, and the overlap in targets used for both antifungal drugs and fungicides exacerbates the situation.
The potential savior, olorofim, currently in phase 3 clinical trials, faces a critical juncture. Sharing its target, an enzyme called dihydroorotate dehydrogenase, with a fungicide called ipflufenoquin, raises concerns about the fungicide’s impact on the drug’s efficacy. A similar narrative looms over fosmanogepix, another novel antifungal awaiting FDA approval, and its potential vulnerability to the fungicide aminopyrifen.
In the battle against antifungal drug resistance, competition with fungicides is only one facet. Poor diagnostic tests, limited infection surveillance, and drug misuse contribute to the crisis. A coordinated effort between regulatory agencies, such as the FDA and the Environmental Protection Agency (EPA), is crucial to navigate this intricate landscape.
Efforts are underway, with the EPA collaborating with the Department of Health and Human Services and the Department of Agriculture to create a framework safeguarding antifungals. The goal is to finalize this framework by the end of the year, ensuring a balance between global food supply and human antifungals.
In conclusion, the journey to combat fungal threats demands collaboration, foresight, and strategic planning. While challenges persist, the potential life-saving impact of new antifungals like olorofim underscores their irreplaceable role in addressing fungal infections. As the world grapples with the intricate dance between medicine and agriculture, the quest for effective antifungal solutions remains more vital than ever.
In the perpetual race against evolving fungal infections, the pharmaceutical industry faces unprecedented challenges in creating effective antifungal drugs. Last summer, the Food and Drug Administration (FDA) dealt a setback to the development of a groundbreaking antifungal drug named olorofim, requesting additional data from the company. This denial marked a crucial moment, as the FDA…