Regulatory Considerations in the Approval of Rezafungin (REZZAYO) for the Treatment of Candidemia and Invasive Candidiasis in Adults

Heidi L Smith; Timothy J Bensman; Shrimant Mishra; Xianbin Li; Cheryl A Dixon; Jalal Sheikh; Owen G McMaster; Abhay Joshi; Daniel B Rubin; Avery Goodwin; Terry J Miller; Zhixia Y Danielsen; Irum Syed; Sunita J Shukla; Dmitri Iarikov; Peter W Kim; John J Farley

doi:10.1093/infdis/jiae146

Regulatory Considerations in the Approval of Rezafungin (REZZAYO) for the Treatment of Candidemia and Invasive Candidiasis in Adults

J Infect Dis. 2024 Mar 19:jiae146. doi: 10.1093/infdis/jiae146. Online ahead of print.

Authors

Heidi L Smith¹, Timothy J Bensman², Shrimant Mishra¹, Xianbin Li³, Cheryl A Dixon³, Jalal Sheikh¹, Owen G McMaster⁴, Abhay Joshi², Daniel B Rubin³, Avery Goodwin¹, Terry J Miller⁴, Zhixia Y Danielsen², Irum Syed⁵, Sunita J Shukla⁶, Dmitri Iarikov¹, Peter W Kim¹, John J Farley⁶

Affiliations

¹ Division of Anti-Infectives, Office of Infectious Diseases, Office of New Drugs, Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
² Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, CDER, FDA, Silver Spring, Maryland, USA.
³ Division of Biometrics IV, Office of Biostatistics, Office of Translational Sciences, CDER, FDA, Silver Spring, Maryland, USA.
⁴ Division of Pharmacology/Toxicology for Infectious Diseases, Office of Infectious Diseases, Office of New Drugs, CDER, FDA, Silver Spring, Maryland, USA.
⁵ DRT Strategies, Inc., Arlington, Virginia, USA.
⁶ Office of Infectious Diseases, Office of New Drugs, CDER, FDA, Silver Spring, Maryland, USA.

PMID: 38502709
DOI: 10.1093/infdis/jiae146

Abstract

On March 22, 2023, the FDA approved rezafungin (REZZAYO) for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options. Rezafungin is an echinocandin that supports weekly dosing, enabling outpatient parenteral treatment that potentially avoids the need for a central venous catheter. Approval of rezafungin was based on a single adequate and well-controlled phase 3 study designed with a Day 30 all-cause mortality primary endpoint and 20% noninferiority margin, which demonstrated that rezafungin is noninferior to the comparator echinocandin. Nonclinical studies of rezafungin in non-human primates identified a neurotoxicity safety signal; however, rezafungin's safety profile in the completed clinical studies was similar to other FDA-approved echinocandins. Here we describe the rationale for this approval and important considerations during the review process for a flexible development program intended to expedite the availability of antimicrobial therapies to treat serious infections in patients with limited treatment options.

Keywords: candidemia; drug approval; echinocandins; invasive candidiasis; rezafungin.

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