Phase III trial of Cresemba (isavuconazonium sulfate) in Candida fungal infections fails to meet primary endpoint- Astellas

Astellas announced topline results from the Phase III ACTIVE study evaluating the efficacy and safety of intravenous (IV) and oral isavuconazole, commercially known as Cresemba (isavuconazonium sulfate), under development for adults with candidemia and other invasive Candida infections. Results from the study demonstrated that the trial did not meet its primary endpoint of non-inferiority in overall treatment response in isavuconazole-treated patients at the end of IV therapy compared to caspofungin. The key secondary endpoint of IV isavuconazole followed by either IV or oral isavuconazole versus IV caspofungin followed by either IV caspofungin or oral voriconazole was comparable between groups.

The overall safety profile for isavuconazole was similar to caspofungin and consistent with safety data seen in the previously reported Phase III studies with isavuconazole. The overall response at the end of IV in the modified intent-to-treat population (N=400) was 60.3% in the isavuconazole treatment group and 71.1% in the caspofungin group with an adjusted treatment difference of -10.8% (95% CI; -19.9%, -1.8%). The lower bound of the 95% confidence interval of the treatment difference between isavuconazole and caspofungin exceeded the pre-specified non-inferiority margin of -15%.

Comment: The FDA has approved the use of Cresemba for patients 18 years of age and older in the treatment of invasive aspergillosis and invasive mucormycosis. In addition, the EU CHMP has recommended the approval of Cresemba for the treatment of adult patients with invasive aspergillosis and adult patients with mucormycosis for whom amphotericin B is inappropriate.