https://orcid.org/0000-0002-1653-2824
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ABSTRACT
Introduction
The epidemiology of invasive Candida infections is evolving. Infections caused by non-albicans Candida spp. are increasing; however, the antifungal pipeline is more promising than ever and is enriched with repurposed drugs and agents that have new mechanisms of action. Despite progress, unmet needs in the treatment of invasive candidiasis remain, and there are still too few antifungals that can be administered orally or that have CNS penetration.
Areas covered
The authors shed light on those antifungal agents active against Candida that are in early- and late-stage clinical development. Mechanisms of action and key pharmacokinetic and pharmacodynamic properties are discussed. Insights are offered on the potential future roles of the investigational agents MAT-2203, oteseconazole, ATI-2307, VL-2397, NP-339, and the repurposed drug miltefosine.
Expert opinion
Ibrexafungerp and fosmanogepix have novel mechanisms of action and will provide effective options for the treatment of Candida infections (including those caused by multiresistant Candida spp). Rezafungin, an echinocandin with an extended half-life allowing for once weekly administration, will be particularly valuable for outpatient treatment and prophylaxis. Despite this, there is an urgent need to garner clinical data on investigational drugs, especially in the current rise of azole-resistant and multidrug-resistant Candida spp.
Article highlights
For the first time in two decades, the antifungal pipeline is loaded and includes several repurposed drugs and drugs with new mechanisms of action.
Ibrexafungerp, a first-in-class triterpenoid antifungal, has recently been FDA-approved for treatment of vulvovaginal candidiasis and may provide an option for treatment of multi-resistant refractory Candida infections or oral step-down treatment.
Rezafungin is an echinocandin with a novel PK profile that allows for once-weekly dosing, which may be of benefit particularly for outpatient treatment or Candida prophylaxis.
Fosmanogepix has a novel mechanism of action with broad spectrum activity and has been granted FDA fast-track for the treatment of invasive candidiasis.
MAT2203 is an encochleated product of amphotericin B, providing systemic exposure after oral administration, and may find a niche in the management of candidiasis.
This box summarizes key points contained in the article.
Acknowledgments
We thank Scynexis, Amplyx/Pfizer, Cidara, and Appili for providing data on activity of their respective antifungals and details on their clinical trials.
Declaration of interest
MH has received research funding from Gilead, Astellas, Pfizer, Merck, Scynexis, F2G, and Amplyx. RS, ME, AA, RK, and ISS have nothing to disclose. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101,037,867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; Consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, and Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, and Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI, and Shionogi; and Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, and Wiley. CLF reports grants, consulting fees, support for travel to meetings, and payment for lectures including service on speakers bureaus from Gilead Sciences, Astellas Pharma, Merck Sharp and Dahme, Basilea, and Angelini. JP has nothing to disclose. GRT has received honoraria from Amplyx, Cidara, Mayne Pharma, Pfizer, and Scynexis. NW has received research funding from Astellas, bioMerieux, F2G, Maxwell Biosciences, and Sfunga. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung), and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees from Ambu GmbH, Gilead Sciences, Mundipharma Research Limited, Noxxon N.V., and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, medupdate GmbH, MedMedia, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital, and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Research Limited, and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office; and Other non-financial interests from Elsevier, Wiley, and Taylor & Francis online outside the submitted work. R.B. has received an IIR grants from Pfizer and from Rokitan, Vienna, Austria, and lecture fees from Gilead and Pfizer. He is a member of an advisory board of Merck Sharp & Dohme. M.C.A. has, over the past 5 years, received research grants/contract work (paid to the SSI) from Amplyx, Basilea, Cidara, F2G, Gilead, Novabiotics and Scynexis, and speaker honoraria (personal fee) from Astellas, Chiesi, Gilead, MSD, and SEGES. She is the current chairman of the EUCAST-AFST. M.M.A. received honoraria from Shionogi and La Jolla pharmaceutical for advisory board meetings. J.R.P. received research grants, advisory board, and consulting fees from Astellas, Appili, Cidara, Matinas, F2G, Scynexis, Pfizer, and Minnetonix. PGP receives research grant support from Cidara, Scynexis, Mayne Pharma, Gilead, and Astellas.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
*Availability of data and material Data available upon request.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.