Olorofim in Treatment of Patients With Poorly Controlled Disseminated Coccidioidomycosis : A Single-Group, Open-Label, Phase 2b, Multicenter Study.

BACKGROUND

Olorofim, a novel dihydroorotate dehydrogenase inhibitor, may be efficacious in patients with disseminated coccidioidomycosis (DCM) who lack alternative treatment options.

OBJECTIVE

To evaluate olorofim effectiveness and adverse events in patients with DCM.

DESIGN

Single-group, open-label, phase 2b study. (ClinicalTrials.gov: NCT03583164).

SETTING

Ten U.S. sites.

PARTICIPANTS

Forty-one patients with DCM and limited or no treatment options. Patients received olorofim alone or in combination with ongoing standard of care during an 84-day main treatment phase. Extended treatment was offered to patients.

MEASUREMENTS: Mycoses Study Group-European Organization for Research and Treatment of Cancer (MSG-EORTC) criteria for global response based on subcategories of clinical, radiologic, and mycologic response were adjudicated by an independent data review committee (DRC) at days 42 and 84 (main treatment phase). Because the slow pace of serologic improvement in DCM limits global response to stable at best, this article focuses on patient clinical responses. Treatment-emergent adverse events (TEAEs) were compiled for both treatment phases.

RESULTS

Forty-one patients with DCM were enrolled from May 2019 to August 2022. Thirty-nine (95.1%) did not have immunosuppression. Central nervous system disease was present in 30 (73.2%) patients, and 13 (43.3%) had a ventriculoperitoneal shunt with or without an Ommaya reservoir. Clinical success as adjudicated by the DRC occurred in 31 of 41 patients (75.6% [95% CI, 59.7% to 87.6%]) at day 42 and 30 of 41 patients (73.2% [CI, 57.1% to 85.8%]) at day 84. The main TEAE was hepatic biochemistry elevation in 9 of 41 patients (21.9%), which was managed by liver enzyme monitoring and dose reduction or pause in 8 patients (19.5%) and drug discontinuation in 1 patient (2.4%).

LIMITATION: This was a single-group, open-label trial, but a randomized controlled trial would be preferable.

CONCLUSION

Olorofim showed effectiveness in patients with DCM with limited or no therapeutic options.

PRIMARY FUNDING SOURCE: F2G, Ltd.