The European Medicines Agency (EMA) has proposed a revision of its guideline on the clinical evaluation of antifungal agents for the treatment and prophylaxis of invasive fungal disease (IFD), aiming to address challenges posed by rare and emerging pathogens, new drug classes, and alternative routes of administration. The concept paper, published on 29 June 2026, outlines updates to the current guideline (CHMP/EWP/1343/01 Rev. 1), which has been in effect since November 2010.
The revision is driven by the development of several new antifungal agents active against rare or emerging pathogens such as Scedosporium spp., Mucorales, and Candida auris, some of which are resistant to existing antifungal classes. The EMA's Infectious Disease Working Party (IDWP) and the Committee for Medicinal Products for Human Use (CHMP) have identified a need to clarify the minimum data package and alternative study designs that could support regulatory claims for these agents, particularly when randomised clinical trials are unfeasible. The concept paper suggests that for rare pathogens, alternative designs such as uncontrolled studies or larger non-inferiority margins may be considered, especially if efficacy evidence from randomised trials in standard indications (e.g., invasive candidiasis or aspergillosis) is available.
Other key updates include alignment with recently updated consensus definitions of IFD and response criteria from the EORTC/MSGERC, as well as the inclusion of a definition for breakthrough infections, which is currently missing. The revision will also address the development of inhaled antifungal agents for lung fungal diseases, for which no specific regulatory expectations exist in the current guideline. Additionally, experience from paediatric investigation plans will be incorporated, and the estimands framework from ICH E9(R1) will be implemented.
The public consultation on the concept paper runs until 30 September 2026. Stakeholders, including pharmaceutical companies developing antifungal agents, clinical researchers, and patient groups, are invited to provide comments via the EUSurvey form. The revised guideline is expected to replace the current version and will impact clinical trial design for new antifungal drugs, potentially reducing development costs for treatments targeting rare IFDs while ensuring robust efficacy data. However, the acceptance of alternative study designs may introduce uncertainty in regulatory decision-making, balancing innovation with evidence standards.