Isavuconazole Noninferior to Voriconazole in Invasive Mold Disease

PHILADELPHIA, PA—The novel, broad-spectrum, triazole antifungal, isavuconazole, has comparable efficacy to voriconazole for the primary treatment of invasive mold disease in patients both with and without neutropenia, according to phase 3 trial results presented at IDWeek 2014.

The agent, available as a water-soluble prodrug in intravenous (IV) and oral formulations for the treatment of invasive fungal disease, may also be better tolerated, said Thomas F. Patterson, MD, of The University of Texas Health Science Center, San Antonio, TX.

In patients with invasive mold disease, “neutropenia is linked to significant morbidity and mortality,” Dr. Patterson explained. He presented the trial's outcomes in patients with and without neutropenia at baseline.

Patients with proven, probable, or possible invasive mold disease, as defined using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, were randomly assigned 1:1 to receive isavuconazole 200mg IV three times daily for 2 days, then 200mg once daily (IV or orally), or voriconazole 6mg/kg IV twice daily on Day 1, 4mg/kg IV twice daily on Day 2, then either 4mg/kg IV twice daily or 200mg orally for twice daily for up to 84 days.

The primary endpoint was all-cause mortality through Day 42. Overall success at end of treatment was determined by an independent data review committee. Neutropenia was defined as per EORTC/MSG criteria.

A total of 163 patients with neutropenia were treated with isavuconazole (88 with proven/probable invasive mold disease) and 175 with voriconazole (73 with proven/probable invasive mold disease). Of those who were non-neutropenic, 94 received isavuconazole (55 with proven/probable invasive mold disease) and 84 (56 with proven/probable invasive mold disease), voriconazole.

All-cause mortality at Day 42 was 21% among patients who were neutropenic for both the isavuconazole and voriconazole arms (adjusted difference -0.2 [-8.7, 8.3]) and, for the non-neutropenic arms, 15% and 18%, respectively (adjusted difference -4.0 [-14.2, 6.2]). Among patients with proven/probable invasive mold disease who were neutropenic, all-cause mortality at day 42 was 25% in the isavuconazole arm and 23% in the voriconazole arm (2.4 [-10.2, 14.9]) and, in the non-neutropenia group, 11% in the isavuconazole arm and 23% in the voriconazole arm (-13.5 [-26.8, -0.3]).

Overall success at end of treatment was comparable, researchers concluded. The rate was 39% of neutropenic patients with proven/probable invasive mold disease treated with isavuconazole compared with 40% of those treated with voriconazole (0.4 [-14.0, 14.7)]. Of those who were non-neutropenic, success was 29% in the isavuconazole arm versus 32% in the voriconazole arm (2.5 [-13.3, 18.2]).

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