Antifungal agents in clinical and preclinical development: overview and analysis
This report presents the first World Health Organization (WHO) analysis of antifungal agents in clinical and preclinical development.
It covers systemic antifungal drugs in development worldwide, including label extension and repurposed products, and critically evaluates how well the current pipeline addresses infections caused by WHO fungal priority pathogens.
The scope of the report is to provide an overview of the current research and development (R&D) landscape and to foster the development of antifungal agents for the most urgent unmet medical needs. This report is part of the WHO’s efforts to monitor, coordinate and strengthen global R&D efforts to address the ongoing void in antimicrobial drug development.
The report also assesses whether the agents in development have in vitro and in vivo data showing no known cross-resistance. When no cross-resistance is observed, the candidate drug is considered potentially innovative for the scope of this review. Surrogate criteria for assessing the innovation potential include belonging to a new chemical class, presenting a novel target, and/or having a new mode of action. These criteria are intended to support and/or explain the observed lack of crossresistance or, in cases where no data on cross-resistance has been generated, predict the potential for a drug to show no cross-resistance.
WHO, along with an expert advisory group on the R&D of novel antifungal treatments, conducted a rigorous evaluation of antifungal agents in clinical and preclinical development. The review process with the expert group involved pre-consultation surveys, in-depth discussions during a one-day virtual meeting, and the use of a newly developed assessment matrix. The report was circulated among all members and observers of the expert group for feedback before publication.
Most approved antifungal drugs commercially available pose challenges, including frequent adverse events, significant drug–drug interactions, limited dosage forms, and the need for prolonged treatment courses (often ‘in-hospital’). Within the range of antifungal medications available to adults, there is a lack of antifungals with a child-friendly formulations for paediatric use.
In the past 10 years, only four new antifungal drugs have been approved by the United States Food and Drug Administration, the European Medicines Agency, or by the Chinese National Medical Products Administration.
All four approved drugs have both in vitro and in vivo data for activity against at least one critical priority pathogen (CPP) according to the WHO Fungal priority pathogens list (FPPL); two candidates have activity against three CPPs, one agent shows activity against two CPPs, and one agent against one CPP.
Three antifungal drugs have in vitro and in vivo evidence of activity against some of the WHO high- and mediumpriority pathogens, also known as other priority pathogens (OPPs).
Only one of the approved drugs meets any of the criterion agreed by WHO to assess innovation.
Three out of the four approved drugs have a reduced risk of DDIs.
Antifungal agents in clinical and preclinical development: overview and analysis
Antifungal pipeline dashboard and data (2024)
WHO fungal priority pathogens list to guide research, development and public health action