SCY-247, a second-generation triterpenoid antifungal, shows low risk for clinically meaningful interactions with CYP3A4 substrates: results from a phase 1 midazolam drug-drug interaction study.

Authors

Stephen Wring, Christopher Argent, Gail Murphy, David Angulo, Michelle Middle

Published in

Antimicrobial agents and chemotherapy. Pages e0096126. Nov 09, 2026. Epub Nov 09, 2026.

Abstract

SCY-247, an oral and intravenous second-generation triterpenoid antifungal, is being developed for treatment and prevention of invasive fungal infections caused by Candida, Aspergillus, and Pneumocystis species. In vitro studies indicated that SCY-247 is metabolized by cytochrome P450 (CYP) 3A4 and 3A5 and that SCY-247 has a lowered potential for CYP450-mediated drug-drug interactions compared with azoles. This phase 1 study in 12 healthy adult participants evaluated the effect of supra-therapeutic repeated doses of SCY-247 on the pharmacokinetics of midazolam, a sensitive substrate of CYP3A4. Participants received midazolam 2 mg oral solution once daily on Day 1 and Day 8. A loading dose of oral SCY-247 300 mg twice daily was administered on Day 3, followed by maintenance dosing of oral SCY-247 300 mg once daily on Days 4 to 9 (for a total of 7 days of SCY-247 dosing). When co-administered with midazolam, SCY-247 was well tolerated in healthy participants, and there were no serious or severe treatment-emergent adverse events. Geometric mean ratios (with and without SCY-247) for the maximum plasma concentration (C_max) and area under the plasma concentration-time curve from 0 to infinity (AUC_0-inf) were 1.26 and 1.44, respectively, classifying SCY-247 as a weak CYP3A4 inhibitor using regulatory criteria. Therefore, SCY-247 displayed weak inhibition of CYP3A4 at supra-therapeutic doses of 300 mg daily, in contrast to posaconazole and voriconazole, which are strong CYP3A4 inhibitors, and isavuconazole, a moderate CYP3A4 inhibitor. These data are supportive of improved clinical management for CYP3A4 drug-drug interactions with SCY-247 when compared to azoles, particularly relevant in the prophylaxis setting.

PMID:
43002077
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

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