{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:41:29Z","timestamp":1789429289905,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ibrexafungerp is a first\u2010in\u2010class triterpenoid antifungal that targets \u03b2\u2010(1,3)\u2010glucan synthase in fungal cell wall development. It is indicated for vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) in adult and post\u2010menarchal pediatric females. The drug was approved in 2021 and 2022 for VVC and RVVC, respectively. Research is ongoing to evaluate the safety of ibrexafungerp in pregnancy and lactation as well as to explore intravenous and oral formulations for invasive candidiasis and invasive aspergillosis. Ibrexafungerp binds and inhibits \u03b2\u2010(1,3)\u2010glucan synthase that is essential for the synthesis of \u03b2\u2010(1,3)\u2010D\u2010glucan, a key polymer in the fungal cell wall, leading to cell lysis and death. This mechanism of action varies from that of the current VVC therapy, fluconazole, which makes ibrexafungerp a primary candidate for treating fluconazole\u2010resistant patient cases. The drug is distributed into vaginal tissue at higher concentrations and has increased efficacy at lower pH compared to fluconazole, indicating a therapeutic advantage for VVC. Ibrexafungerp was generally well\u2010tolerated in most participants throughout clinical trials. The most commonly reported treatment\u2010emergent adverse events were headache, dizziness, and gastrointestinal\u2010related effects. The efficacy of ibrexafungerp was found to be comparable to fluconazole and superior to placebo as seen in key clinical trials: DOVE (NCT03253094) and VANISH303 (NCT03734991). We reviewed the regulatory approval process of ibrexafungerp, including key clinical trials and in\u2010depth analyses of pivotal studies related to the drug's clinical efficacy and safety. Additionally, we reviewed the drug's unique mechanism of action and the pharmacokinetic and pharmacodynamic characteristics essential for its use in VVC and RVVC.<\/jats:p>","DOI":"10.1111\/cts.70362","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T12:35:02Z","timestamp":1758285302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ibrexafungerp: Mechanism of Action, Clinical, and Translational Science"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3274-1976","authenticated-orcid":false,"given":"Adelynne H.","family":"Walley","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy University of Montana  Missoula Montana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-8737","authenticated-orcid":false,"given":"Lauren N.","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy University of Montana  Missoula Montana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-4140","authenticated-orcid":false,"given":"Erica L.","family":"Woodahl","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy University of Montana  Missoula Montana USA"},{"name":"L.S. Skaggs Institute for Health Innovation University of Montana  Missoula Montana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7288-5196","authenticated-orcid":false,"given":"Shayna R.","family":"Killam","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy University of Montana  Missoula Montana USA"},{"name":"L.S. Skaggs Institute for Health Innovation University of Montana  Missoula Montana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"issue":"27","key":"e_1_2_12_2_1","first-page":"1","article-title":"Vulvovaginal Candidiasis: A Current Understanding and Burning Questions","volume":"6","author":"Willems H. M. E.","year":"2020","journal-title":"Journal of Fungi"},{"key":"e_1_2_12_3_1","article-title":"Candida Infections and Their Prevention","volume":"2013","author":"Kabir A. M.","year":"2012","journal-title":"ISRN Preventive Medicine"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.906563"},{"key":"e_1_2_12_5_1","volume-title":"BREXAFEMME (ibrexafungerp)","year":"2022"},{"key":"e_1_2_12_6_1","unstructured":"UpToDate Inc. \u201cLexi\u2010Drugs Online Database \u201daccessed July 23 2025 http:\/\/online.lexi.com."},{"key":"e_1_2_12_7_1","unstructured":"Merative \u201cMicromedex RED BOOK Online Database \u201daccessed July 23 2025 https:\/\/www.micromedexsolutions.com\/."},{"key":"e_1_2_12_8_1","unstructured":"D.Matecka \u201cApproval Package for Application Number: 214900Orig1s000 Product Quality Review(s) \u201d(2021) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2021\/214900Orig1s000ChemR.pdf."},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.14333"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof7030163"},{"key":"e_1_2_12_11_1","unstructured":"P. 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I.Sherwat \u201cApproval Package for: Application Number: 214900Orig1s000 BREXAFEMME \u201dhttps:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2021\/214900Orig1s000Approv.pdf."},{"key":"e_1_2_12_13_1","unstructured":"\u201cClinicalTrials.gov \u201daccessed July 10 2025 https:\/\/clinicaltrials.gov\/search?intr=Ibrexafungerp."},{"key":"e_1_2_12_14_1","unstructured":"\u201cSCYNEXIS Announces Successful Completion of Phase 1 Trial Evaluating Intravenous (IV) Formulation of Ibrexafungerp \u201daccessed September 6 2024 https:\/\/ir.scynexis.com\/news\u2010events\/press\u2010releases\/detail\/260\/scynexis\u2010announces\u2010successful\u2010completion\u2010of\u2010phase\u20101\u2010trial."},{"key":"e_1_2_12_15_1","unstructured":"Food and Drug Administration \u201cQualified Infectious Disease Product Designation\u2014Questions and Answers: Guidance for Industry \u201d(2021)."},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.588"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02068-16"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02119-18"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02611-18"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab841"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz277"},{"issue":"2","key":"e_1_2_12_22_1","first-page":"S73","article-title":"Oral Ibrexafungerp Outcomes by Fungal Disease in Patients From an Interim Analysis of a Phase 3 Open\u2010Label Study (FURI)","volume":"9","author":"Thompson G. 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