In vitro Activity of Isavuconazole against Cryptococcus Isolates – A Pooled Analysis from 3 Studies

Ref ID: 18718

Author:

J. I. Smart, PhD – Clinical Microbiology Project Manager1, M. E. Jones, PhD – Basilea Patent Officer 2, L. L. Kovanda, N/A – Director, Global Development Project Leader (GDPL), Infectious Diseases 1;

Author address:

1Astellas Pharma Global Dev., Inc, Deerfield, IL, 2Basilea Pharmaceutica Intl. Ltd., Basel, Switzerland.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Objectives: Cryptococcosis is an invasive fungal infection caused by Cryptococcus gattii and 2 varieties of C. neoformans (C. neoformans var neoformans and C. neoformans var grubii). Isavuconazole (ISA; BAL8557) is a novel broad-spectrum water soluble triazole agent with IV and oral formulations currently in Phase 3 clinical trials for the treatment of invasive Aspergillus, Candida, and rare mould infections. The active moiety of ISA, BAL4815 has been shown to have in vitro antifungal activity against clinically relevant species of yeasts and moulds including Cryptococcus species. Methods: We examined the in vitro activity of ISA against isolates of C. neoformans var neoformans (C. neoformans), C. neoformans var grubii (C. grubii), and C. gattii (Table). These data represent a compilation of MIC data for ISA, voriconazole (VRC) and posaconazole (PSC) from 3 individual EU and US studies. All MIC data in the pooled analysis were derived using CLSI (M38-A) methodology with MICs evaluated at 72 h. Results: Overall, ISA was the most active of the triazoles against the Cryptococcus isolates tested, especially against C. gattii where the highest MIC recorded was 0.06 mg/L compared with 0.25 mg/L (VRC) and 0.125 mg/L (PSC). The MIC50 and MIC90 results for ISA were equal to or 2-fold lower than those measured for VRC, and PSC for the Cryptococcus species tested (Table). Conclusions: These results demonstrate the potent in vitro activity of ISA against a diverse range of Cryptococcus isolates. The ISA MICs were several fold lower than the anticipated trough levels reached with the dose regimen tested in the ongoing Phase 3 studies. Its potent in vitro activity, predictable pharmacokinetics, good oral bioavailability and anticipated penetration into the CNS suggest ISA is a promising new antifungal agent.

Abstract Number: M-331

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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