MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis
Abstract
Objectives: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population. Methods: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. Results: Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. Conclusions: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.
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Ibrexafungerp is currently only FDA approved as oral therapy for vulvovaginal candidiasis.
“Ibrexafungerp is currently only FDA approved as oral therapy for vulvovaginal candidiasis, although clinical trials for invasive candidiasis step-down therapy, refractory candidiasis, and C. auris are ongoing.149,156–159”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [158]
Ibrexafungerp has oral bioavailability of 35-50% and good systemic distribution except for the CNS.
“It has oral bioavailability of 35–50% and good systemic distribution except for the CNS.”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [158]
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- Authors
- Spec, A., Pullman, J., Thompson, G. R., Powderly, W. G., Tobin, E. H., Vazquez, J., Wring, S. A., Angulo, D., Helou, S., Pappas, P. G., Mycoses Study Group, Vasquez, J., Ostrosky-Zeichner, L., Patterson, T., Alexander, B., Boucher, H., Pappas, P., Betts, R., Schuster, M., Shoham, S., Revankar, S., Mushatt, D., Bedimo, R., Freifeld, A., Nguyen, M. H., Mylonakis, E., Kett, D., Reboli, A., Walsh, T., Pouch, S., Almyroudis, N., Andes, D., Hadley, S., Barron, M., Mullane, K., & Miller, L.
- Affiliations
- Washington University in St. Louis (US)
- Mercury Street Medical, Butte, MT, USA
- University of California, Davis (US)
- Albany Medical Center Hospital (US)
- Medical College of Georgia/Augusta University, Augusta, GA, USA
- Scynexis (United States) (US)
- University of Alabama, Birmingham, AL, USA
- Augusta University (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Spec, Andrej
- ORCID
- Spec, Andrej
- Thompson, George R
- Powderly, William G
- Tobin, Ellis H
- Patterson, Thomas
- Alexander, Barbara
- Schuster, Mindy
- Shoham, Shmuel
- Revankar, Sanjay
- Mushatt, David
- Bedimo, Roger
- Freifeld, Alison
- Nguyen, Minh Hong
- Mylonakis, Eleftherios
- Reboli, Annette
- Walsh, Thomas
- Pouch, Stephanie
- Almyroudis, Nikolaos
- Andes, David
- Hadley, Susan
- Barron, Michelle
- Miller, Loren
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-07-15
- Volume
- 74
- Issue
- 10
- Pages
- 3056-3062
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- OpenAlex
- W2961594003
- Cited by
- 88
- References
- 16
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 24 · 2023: 14 · 2022: 11 · 2021: 16 · 2020: 8 · 2019: 1
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Scynexis
- Inc
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- ibrexafungerp, invasive candidiasis, oral antifungal therapy, echinocandin therapy, step-down therapy, dosing regimen, population pharmacokinetics, fluconazole, micafungin, non-neutropenic patients, treatment efficacy and safety
- MeSH terms
- Micafungin, Administration, Oral, Adult, Aged, Antifungal Agents, Candida, Female, Glycosides, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Triterpenes, Fluconazole, Echinocandins, Candidiasis, Invasive
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