Isavuconazole (ISA) is a novel, water-soluble, broad-spectrum triazole antifungal agent developed for the treatment of invasive fungal diseases (IFDs), including invasive aspergillosis. These are rare infections that occur typically in immunocompromised, critically ill patients. By disrupting fungal membrane structure and function, ISA is active against all major opportunistic and pathologic fungi [Seyedmousavi S et al. Expert Rev Anti Infec Ther. 2015]. ISA was approved by the FDA for the treatment of aspergillosis and mucormycosis in March 2015.

The SECURE trial [NCT00412893] investigated the safety and efficacy of ISA as compared with voriconazole (VRC) in patients with IFD caused by Aspergillus spp and other filamentous fungi. SECURE was a large (n = 516) phase 3 double-blind randomized trial that demonstrated the noninferiority of ISA compared with VRC for all-cause mortality at day 42 in the intention-to-treat population (ISA, 18.6%; VRC, 20.2%; 95% CI, −7.8 to 5.7) [Maertens J et al. ECCMID 2014 (abstr O230a)].

Two presenters in this session reported additional, more detailed safety and outcomes data from SECURE. Andrew J. Ullmann, MD, University of Würzburg, Würzburg, Germany, presented information regarding the development of treatment-emergent adverse events (TEAEs) in both the ISA and VRC groups. A TEAE was defined as any adverse event after the first administration of the drug until 28 days following the last administration.

Among patients in the ISA group, 96% experienced at least 1 TEAE, compared with 98% in the VRC group. This was an expected finding related to the severity of the patients’ underlying illnesses. However, when analyzed by system organ class, moderate or severe TEAEs in the ISA group were lower in 19 of the 24 classes. In the comparison of the ISA and VRC groups, a significant difference was seen in disorders of the eye (15% vs 27%; P < .01), skin (33% vs 42%; P < .05), and hepatobiliary system (9% vs 16%; P < .05). Overall, the rate of treatment-related TEAEs was significantly lower in the ISA group than the VRC group (42% vs 60%, P < .01). Psychiatric (27% vs 33%) and cardiac (17% vs 22%) events were also lower in the ISA group vs the VRC group; however, this difference was not statistically significant.

Prof Ullmann suggested that the difference in TEAEs favoring ISA was influenced primarily by 4 factors: disorders of the eye, the hepatobiliary system, investigations (including elevations in hepatic enzymes), and psychiatric disorders.

Debra Goff, PharmD, Ohio State University, Columbus, Ohio, USA, presented safety and outcomes in obese patients (body mass index [BMI] ≥ 30 kg/m²) enrolled in the SECURE trial. The analysis was done on patients with proven/probable IFD treated with either ISA or VRC who were categorized into 3 BMI classifications: < 25, 25 to < 30, and ≥ 30 kg/m².

Of the 527 randomized patients, 263 had proven/probable IFD and BMI data available; 25 patients were obese (ISA, n = 15; VRC, n = 10). All-cause mortality through day 42 was comparable between treatment arms in obese patients (1 vs 2 patients; adjusted difference, –13.3; 95% CI, −50.9 to 24.2). Similar numbers of obese patients responded successfully to either ISA or VRC (6 vs 4; adjusted difference, 0.0; 95% CI, −49.4 to 49.4). Drug-related TEAEs (40% vs 70%), serious TEAEs (53% vs 90%), and deaths (27% vs 40%) were less frequent in obese patients treated with ISA compared with VRC.

Dr Goff concluded that in this small subgroup of obese patients, ISA outcomes were comparable with VRC and similar to those of the other BMI subgroups. Among a small group of obese patients, there were fewer drug-related TEAEs, serious TEAEs, and deaths reported in those treated with ISA vs VRC.