FDA Public Workshop Summary-Addressing Challenges in Inhaled Antifungal Drug Development

Caroline J Jjingo; Shukal Bala; Ursula Waack; Mark Needles; Timothy J Bensman; Owen McMaster; Thomas Smith; Brandon Blakely; Irene Z Chan; Khalid Puthawala; Cheryl Dixon; Yongman Kim; Robert Lim; Philip Colangelo; Christopher St Clair; Sumathi Nambiar; Richard B Moss; Radu Botgros; Rohit Bazaz; David W Denning; Kieren A Marr; Shahid Husain; Lance Berman; Dale J Christensen; Charlotte Keywood; Russell G Clayton; Thomas J Walsh; Hyo Sook E Song; Sunita J Shukla; John J Farley

doi:10.1093/cid/ciad607

FDA Public Workshop Summary-Addressing Challenges in Inhaled Antifungal Drug Development

Clin Infect Dis. 2023 Oct 6:ciad607. doi: 10.1093/cid/ciad607. Online ahead of print.

Authors

Caroline J Jjingo¹, Shukal Bala¹, Ursula Waack¹, Mark Needles¹, Timothy J Bensman², Owen McMaster³, Thomas Smith¹, Brandon Blakely⁴, Irene Z Chan⁵, Khalid Puthawala⁶, Cheryl Dixon⁷, Yongman Kim⁸, Robert Lim⁶, Philip Colangelo², Christopher St Clair⁹, Sumathi Nambiar¹, Richard B Moss¹⁰, Radu Botgros¹¹, Rohit Bazaz¹², David W Denning¹³, Kieren A Marr¹⁴, Shahid Husain¹⁵, Lance Berman¹⁶, Dale J Christensen¹⁷, Charlotte Keywood¹⁸, Russell G Clayton¹⁹, Thomas J Walsh²⁰, Hyo Sook E Song²¹, Sunita J Shukla²², John J Farley²²

Affiliations

¹ Division of Anti-Infectives, Office of Infectious Diseases, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
² Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
³ Division of Pharmacology/Toxicology for Infectious Diseases, Office of Infectious Diseases, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
⁴ Division of ENT, Sleep, Respiratory, and Anesthesia, Office of Health Technology 1, Office of Product Evaluation and Quality, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland, USA.
⁵ Division of Medication Error Prevention and Analysis, Office of Medication Error Prevention and Risk Management, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
⁶ Division of Pulmonology, Allergy and Critical Care, Office of Immunology and Inflammation, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
⁷ Division of Biometrics IV, Office of Biostatistics, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
⁸ Division of Biometrics III, Office of Biostatistics, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
⁹ Division of Clinical Outcome Assessment, Office of Drug Evaluation Science, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
¹⁰ Department of Pediatrics, Lucile Packard Children's Hospital and Stanford Children's Health, Stanford University Medical Center, Palo Alto, California, USA.
¹¹ Office of Biological Health Threats and Vaccines Strategy, European Medicines Agency, Amsterdam, the Netherlands.
¹² Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
¹³ Chief Executive, Global Action Fund for Fungal Infections, The University of Manchester, Manchester, UK.
¹⁴ Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁵ Transplant Infectious Diseases Clinic, University Health Network, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Pulmocide, London, United Kingdom.
¹⁷ TFF Pharmaceuticals, Fort Worth, Texas, USA.
¹⁸ Zambon SpA, Milano, Italy.
¹⁹ Aeremedea, LLC, Fenandina Beach, Florida, USA.
²⁰ Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medicine, New York, New York, USA; Save Our Sick Kids Foundation, New York, New York, USA.
²¹ DRT Strategies, Arlington, Virginia, USA.
²² Office of Infectious Diseases, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.

PMID: 37802928
DOI: 10.1093/cid/ciad607

Abstract

Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On September 25, 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.

Keywords: antifungal agents; asthma; drug development; rare diseases.