Cresemba isavuconazonium: Phase III data

The double-blind, international Phase III ACTIVE trial in 440 patients with candidemia and other invasive Candida infections showed that IV isavuconazole missed the primary endpoint of non-inferiority to IV Cancidas caspofungin in overall treatment response at the end of IV treatment. Specifically, in the modified intent-to-treat (mITT) population (n=400), the overall treatment response at the end of the IV treatment was 60.3% for isavuconazole vs. 71.1% for Cancidas (95% CI: -19.9% vs. -1.8%). The lower bound of the 95% CI of the treatment difference exceeded the pre-specified non-inferiority margin of -15%. Patients received either a loading dose of 200 mg IV isavuconazole every 8 hours for the first 48 hours followed by a once-daily maintenance dose of 200 mg IV isavuconazole from day 3 to day 10 or a loading dose of 70 mg IV Cancidas on day 1 followed by a once-daily maintenance dose of 50 mg IV Cancidas from day 2 to day 10. At day 10, patients had the option to continue IV therapy or switch to oral therapy. Isavuconazole patients were switched to once-daily 200 mg oral isavuconazole and Cancidas patients were switched to twice-daily 400 mg oral Vfend voriconazole. Isavuconazole led to an overall treatment response rate of 54.8% at 2 weeks after the end of treatment vs. 57.2% in the Cancidas/Vfend group (95% CI: -12.2% vs. 6.8%). Additionally, the secondary endpoint of all-cause mortality was comparable at days 14 and 56 in both treatment arms. ...