Structural barriers to antifungal drug development

Fungal diseases represent a growing yet under-recognized global health threat, with mortality comparable to major infectious diseases but a disproportionately weak therapeutic pipeline. This review examines the antifungal innovation gap as a systemic phenomenon shaped by intertwined scientific, economic, and societal constraints. While multidrug-resistant pathogens underscore the urgent need for new antifungal agents, progress is hindered by fungal-human cellular similarity, high development costs, limited commercial incentives, and toxicity concerns. Agricultural fungicide practices that drive resistance and intellectual-property regimes that restrict affordability and generic entry further complicate this landscape. These scientific and economic barriers coexist with profound inequities in global access to existing antifungals, revealing a persistent gap between therapeutic availability and public health needs. The resulting public-health consequences include delayed treatment, reliance on suboptimal therapies, and widening disparities in outcomes across low-resource settings. This review proposes that antifungal agents should be conceptualized as global public goods and that non-profit development models offer a promising pathway to overcome current bottlenecks. An integrated perspective across clinical, agricultural, regulatory, and public-health domains underscores the need for coordinated strategies to restore innovation, ensure equitable access, and strengthen global preparedness against fungal diseases.