| Title: |
Compassionate Use of Olorofim for Invasive Mold Infections: A Nationwide Observational Study in France |
| Authors: |
Esnault, V; Godet, C.; Garcia-Hermoso, D; Charmillon, Alexandre; Parize, P; Bonnal, C.; Debourgogne, Anne; Morio, F; Bougnoux, M.E.; Dannaoui, E.; Bellanger, A.P.; Gangneux, J.P.; Sendid, B.; Cardot, E.; Melenotte, C.; Rouzaud, C.; Lefort, A.; Colin de Verdiere, S.; Brugiere, O.; Tetart, M; Eschapasse, E.; Berceanu, A; Tattevin, P.; Levy, R.; Faure, E.; Lanternier, F |
| Contributors: |
CHU Henri Mondor Créteil; Groupe Henri Mondor-Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); CHU Tenon AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); SOrbonne study group for Lung Infectious Diseases (GRC 40 : Solid); Sorbonne Université (SU); Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); AP-HP - Hôpital Bichat - Claude Bernard Paris; Stress, Immunité, Pathogènes (SIMPA); Université de Lorraine (UL); Cibles et Médicaments des Infections et de l'Immunité - UR 1155 (IICiMed); Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Université Paris Cité (UPCité); Laboratoire Chrono-environnement (UMR 6249) (LCE); Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC); Université Bourgogne Franche-Comté COMUE (UBFC)-Université Bourgogne Franche-Comté COMUE (UBFC); Institut de recherche en santé, environnement et travail (Irset); Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF); Université de Lille-Centre National de la Recherche Scientifique (CNRS); Hôpital Foch Suresnes; Hôpital Beaujon AP-HP; Centre Hospitalier de Tourcoing; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS); Centre d'infectiologie Necker-Pasteur CHU Necker; Institut Pasteur Paris (IP)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité) |
| Source: |
ISSN: 2328-8957. |
| Publisher Information: |
CCSD; Oxford University Press |
| Publication Year: |
2026 |
| Subject Terms: |
olorofim; invasive pulmonary aspergillosis; fungal infections; fungal diseases; antifungal agents; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology |
| Description: |
International audience ; Background: The increasing incidence of resistant invasive mold infections (IMIs) has highlighted the need for novel antifungal agents. Olorofim, a first-in-class orotomide, has shown promising efficacy in a recent phase II study, but clinical data remain limited.Methods: We conducted a retrospective multicenter cohort study in France, including all patients who received olorofim under compassionate use for proven or probable non-Mucorales IMIs. Eligible patients had IMIs refractory to or intolerance to standard antifungals or no effective treatment options. Efficacy was defined as mycological and clinical control of infection; safety was also assessed.Results: Between January 2020 and December 2023, 17 patients (median age, 39 years) received olorofim. Underlying conditions included primary immunodeficiency (n = 4) and lung transplantation (n = 5). Sites of infection included the lung (88.2%) and the central nervous system (23.5%), with 5 cases of disseminated disease. In total, 23 strains were identified, mostly Aspergillus fumigatus (34.8%) and Microascus spp (13%). The median duration of prior antifungal therapy was 9.1 months. Olorofim was used primarily for refractory IMIs (70.6%) and in combination with other antifungals in 82.4% of cases. Olorofim minimum inhibitory concentrations were ≤0.5 mg/L in the 8 available isolates. Among 15 evaluable patients, 5 (33.3%) achieved clinical and mycological success, 7 (46.7%) had partial responses, and 3 (20%) experienced treatment failure. The 3-month mortality rate was 29.4% (5 of 17). No severe adverse events were reported.Conclusions: Olorofim exhibited potential efficacy and good tolerability in patients with refractory IMIs. Further data from ongoing clinical trials are needed to confirm these findings. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41531505; PUBMED: 41531505; PUBMEDCENTRAL: PMC12794007 |
| DOI: |
10.1093/ofid/ofaf750 |
| Availability: |
https://hal.science/hal-05512639; https://hal.science/hal-05512639v1/document; https://hal.science/hal-05512639v1/file/ofaf750.pdf; https://doi.org/10.1093/ofid/ofaf750 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.87B224C6 |
| Database: |
BASE |