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

Area of Science:

• * Infectious Diseases
• * Mycology
• * Clinical Pharmacology

Background:

• * Rising incidence of antifungal-resistant invasive mold infections (IMIs) necessitates novel therapeutic agents.
• * Olorofim, a novel orotomide antifungal, demonstrates potential but requires further clinical validation.
• * Limited clinical data exist for olorofim in treating complex IMIs.

Purpose of the Study:

• * To evaluate the efficacy and safety of olorofim in patients with refractory non-Mucorales IMIs.
• * To assess clinical and mycological outcomes in patients treated with olorofim under compassionate use.
• * To characterize patient populations and pathogens associated with olorofim use in IMIs.

Main Methods:

• * Retrospective, multicenter cohort study in France.
• * Included patients with proven or probable non-Mucorales IMIs refractory to or intolerant of standard antifungals.
• * Efficacy defined by mycological and clinical infection control; safety also assessed.

Main Results:

• * 17 patients received olorofim for refractory IMIs, primarily affecting the lungs and CNS.
• * Aspergillus fumigatus and Microascus spp. were common pathogens.
• * 33.3% achieved clinical and mycological success; 46.7% had partial responses. 3-month mortality was 29.4%.

Conclusions:

• * Olorofim demonstrated potential efficacy and good tolerability in a challenging patient cohort with refractory IMIs.
• * Further data from ongoing clinical trials are essential to confirm these preliminary findings.
• * Olorofim represents a potential new option for managing difficult-to-treat invasive mold infections.