# Compassionate Use of Olorofim for Invasive Mold Infections: A Nationwide Observational Study in France

## TL;DR

This study examines the real-world use of olorofim for treating mold infections that don't respond to standard treatments, showing some effectiveness and good safety.

## Contribution

First real-world observational study of olorofim for non-Mucorales invasive mold infections under compassionate use.

## Key findings

- 33.3% of patients achieved clinical and mycological success with olorofim.
- Olorofim showed good tolerability with no severe adverse events reported.
- 3-month mortality rate was 29.4% among patients treated with olorofim.

## Abstract

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.

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.

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.

Olorofim exhibited potential efficacy and good tolerability in patients with refractory IMIs. Further data from ongoing clinical trials are needed to confirm these findings.

This first report of olorofim use in real-world clinical practice highlights the promising efficacy and good tolerability of olorofim in patients with invasive mold infections unresponsive to standard therapies, supporting its potential role in difficult-to-treat cases.