New antifungals for the treatment of invasive mould disease

Invasive fungal infections are emerging as a critical threat to healthcare, yet the disparity in development and approval of new antifungal agents has only recently been addressed. In 2022, the WHO published the first global priority list of fungal pathogens (Fungal Priority Pathogens List) in order to promote public health awareness, encourage research and development, and propose actions and strategies for stakeholders to target in combatting the rise of fungal infections.

This review provides a summary of recent data of recently approved and/or investigational antifungals targeted at invasive mould infections, collating updated information on clinical findings of antifungal agents with potential use or activity against moulds listed on the WHO Fungal Priority Pathogens List.

A PubMed literature search 'Aspergillus fumigatus', 'Fusarium', 'Mucorales', 'Eumycetoma', 'Scedosporium', and 'Lomentospora' with names of antifungal agents 'rezafungin', 'ibrexafungerp', 'oteseconazole', 'opelconazole', 'fosmanogepix', 'olorofim', 'BAL2062', 'mandimycin', 'ATI-2307', 'MAT2203', 'TFF voriconazole', and 'miltefosine' was conducted.

Preclinical and clinical trial data published within the last 5 years are discussed. The recent approvals of three new antifungals by the US Food and Drug Administration are a significant accomplishment in the advancement of antifungal therapies. Approvals, current indications, and investigations for rezafungin, ibrexafungerp, and oteseconazole as antimould agents are discussed. Additionally, information on fosmanogepix, opelconazole, and olorofim, as well as reformulated agents and those in the pipeline, is included. Clinical data, where available, were the primary focus of the article.

Development of new antifungal agents is challenging because of limited target sites, emergence of resistance, and adverse toxicity profiles. However, clinical data from fosmanogepix, olorofim, and encochleated amphotericin B are promising in both clinical efficacy and safety for the treatment of invasive mould infections. These new agents offer alternative options for difficult-to-treat infections, while providing promising efficacy and improved safety outcomes.