Clinical experience with isavuconazole in healthy volunteers and patients with invasive aspergillosis in China, and the results from an exposure-response analysis

Background Isavuconazole is a broad-spectrum triazole for the treatment of invasive fungal disease (IFD). Objective To investigate the clinical experience with isavuconazole in Chinese individuals. Patients/Methods Participants were Chinese healthy volunteers from a Phase I pharmacokinetics (PK) and safety study of single/multiple doses of isavuconazole (n = 36) and Chinese patients from the global Phase III SECURE study that assessed safety and efficacy of isavuconazole vs voriconazole for IFD treatment (n = 26). Results No clinically relevant differences in PK were found between Chinese and Western participants, although exposure was increased in Chinese volunteers. Treatment-emergent adverse events (TEAEs) were reported in 75.0% of healthy volunteers, many of which were infusion-related. No serious AEs were reported. In SECURE, findings in Chinese patients (n = 26) were similar to the global population. For patients who received >= 1 dose of study drug, allcause mortality from first dose to Day 42 was 10.0% (1/10) with isavuconazole and 25.0% (4/16) with voriconazole (treatment difference [95% confidence interval, CI]: -15.0% [-43.2%, 13.2%]). Overall response at the end of treatment for patients with proven/probable IFD was 25.0% and 16.7% with isavuconazole and voriconazole, respectively (treatment difference [95% CI] -8.3% [-60.2%, 43.5%]). Isavuconazole was associated with lower incidence of hepatobiliary, eye, skin, subcutaneous tissue and psychiatric disorders compared with voriconazole and lower incidence of treatment-related TEAEs, serious TEAES or death overall. Conclusions Although further research is required, this study demonstrated a favourable risk-benefit profile of isavuconazole in Chinese patients.

Automated summary

The study showed that there were no clinically relevant PK differences between Chinese and Western participants, although Chinese volunteers had higher exposure. In Chinese patients, the efficacy and safety of isavuconazole were similar to the global population.