OBJECTIVES: Invasive aspergillosis (IA) causes nearly 9,000 annual US inpatient hospitalizations, with an associated cost of > $80,000 per admission. Olorofim is an orally administered selective inhibitor of fungal dihydroorotate dehydrogenase in development for the treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory or intolerant to currently available therapy. This research explores the cost-effectiveness of olorofim compared to best available antifungal therapy (BAAT).

METHODS: Using a three-state Markov model, outcomes were simulated over 1 year. Probabilities of antifungal response, mortality, and treatment emergent adverse events (TEAEs) (hepatotoxicity, nephrotoxicity) were based upon 101 patients with proven IA or probable pulmonary IA from an open-label, single-arm P2b olorofim study (NCT03583164) and IA salvage data from Walsh et al., Clin Infect Dis 44:2-12, 2007. Model parameters included healthcare utilization costs in 2023 USD (antifungal agents, ICU days, general ward days, TEAE management), quality-adjusted life years (QALYs) estimated using EQ-5D-5L utilities for success and failure from the P2b study data, and an olorofim proxy price the same as that of liposomal amphotericin B. One-way (OWSA) and probabilistic sensitivity analyses (PSA) were performed to test the model’s robustness.

RESULTS: Estimated 1-year costs of treating proven or probable IA in patient lacking suitable alternative options were $165,532 (olorofim) and $229,589 (BAAT), for an incremental cost of -$64,058. QALYs were 0.47 and 0.23, respectively, making olorofim the dominant (less costly, more effective) strategy. These conclusions were maintained in all OWSA scenarios and in PSA; olorofim was cost-effective in >99% of 1,000 iterations compared to BAAT assuming a willingness-to-pay threshold of $50,000/QALY.

CONCLUSIONS: This analysis suggests that olorofim is cost-effective compared to BAAT for treating proven or probable IA lacking suitable alternative antifungal options from a US payer perspective.