Sistema de Salut de Catalunya
Institut Català de la Salut
[Pappas PG] Division of Infectious Diseases, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. [Vazquez JA] Division of Infectious Disease, Department of Medicine, Medical College of Georgia/Augusta University, Augusta, GA, USA. [Oren I] Infectious Disease Unit, Rambam Health Care Campus, Haifa, Israel. [Rahav G] Sheba Medical Center, Ramat Gan, Israel. Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. [Aoun M] Department of Internal Medicine, Institut Jules Bordet, Brussels, Belgium. [Bulpa P] Intensive Care Medicine, University Hospital Mont-Godinne, CHU UCL Namur, Yvoir, Belgium. [Ferrer R] Grup de Recerca de Shock, Disfunció Orgànica i Ressuscitació (SODIR), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-10-11T12:21:59Z
2023-10-11T12:21:59Z
2023-10
Safety; Antifungal; Candidaemia
Seguridad; Antifúngico; Candidemia
Seguretat; Antifúngic; Candidèmia
Background Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. Methods This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST. Results Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002–0.03 mg/L). Conclusions Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment.
The study was funded by Amplyx, now a subsidiary of Pfizer Inc.
Article
Published version
English
Candidiasi - Tractament; Avaluació de resultats (Assistència sanitària); Medicaments antifúngics - Ús terapèutic; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; DISEASES::Bacterial Infections and Mycoses::Infection::Sepsis::Fungemia::Candidemia; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antifungal Agents; Other subheadings::Other subheadings::/therapeutic use; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento; ENFERMEDADES::infecciones bacterianas y micosis::infección::sepsis::fungemia::candidemia; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antifúngicos; Otros calificadores::Otros calificadores::/uso terapéutico
Oxford University Press
Journal of Antimicrobial Chemotherapy;78(10)
https://doi.org/10.1093/jac/dkad256
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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