Compassionate Use of Olorofim for Invasive Mold Infections: A Nationwide Observational Study in France
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Open Forum Infectious Diseases
DOI: 10.1093/ofid/ofaf750
Authors: V Esnault, C Godet, D Garcia-Hermoso, A Charmillon, P Parize, C Bonnal, A Debourgogne, F Morio, M E Bougnoux, E Dannaoui, A P Bellanger, J P Gangneux, B Sendid, E Cardot, C Melenotte, C Rouzaud, A Lefort, S Colin de Verdiere, O Brugiere, M Tetart, E Eschapasse, A Berceanu, P Tattevin, R Levy, E Faure, F Lanternier
Institutions: Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Sorbonne Université, Hôpital Tenon, SoLID : SOrbonne study group for Lung Infectious Diseases, Institut Pasteur, Université Paris Cité, Centre Hospitalier Régional et Universitaire de Nancy, Hôpital Necker-Enfants Malades, Hôpital Bichat-Claude-Bernard, Stress, IMmunité, PAthogènes, Université de Lorraine, Centre Hospitalier Universitaire de Nantes, Cibles et Médicaments des Infections et de l'Immunité, Nantes Université, Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire de Besançon, Laboratoire Chrono-Environnement, Université de Franche-Comté, Inserm, École des Hautes Études en Santé Publique, Institut de Recherche en Santé, Environnement et Travail, Centre Hospitalier Universitaire de Rennes, Université de Rennes, Université de Lille, Centre Hospitalier Universitaire de Lille, Unité de Glycobiologie Structurale et Fonctionnelle, Hôpital Foch, Hôpital Beaujon, Centre Hospitalier de Tourcoing, Institut du Thorax, Hôpital Pontchaillou, Institut des Maladies Génétiques Imagine, Institut Pasteur de Lille, Center for Infection and Immunity of Lille
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,053
OpenAlex ID: W4417261047