Isavuconazole is a triazole derivative that weakens the structure and function of the fungal cell membrane. It inhibits the enzyme lanosterol 14-alpha-demethylase, preventing conversion of lanosterol to ergosterol. Ergosterol is a key component of the fungal cell membrane.
Cresemba is available as a powder for concentrate for solution for infusion and as hard capsules. Switching between intravenous treatment and oral therapy is appropriate when clinically indicated.
Invasive mucormycosis is an aggressive fungal disease with a poor prognosis; mortality rates can reach 70%. Patients with invasive mucormycosis are often refractory or intolerant to primary antifungal treatment.
In the open-label uncontrolled VITAL trial, the overall success rate in patients with proven or probable mucormycosis treated with isavuconazole (n=37) was 31.4% in those who received the drug as primary antifungal treatment and 36.4% in patients refractory to prior antifungal treatment.
The SECURE trial enrolled 527 patients with invasive aspergillosis. Investigators compared isavuconazole (200mg intravenously three times daily for two days followed by 200mg once daily either intravenously or orally) with voriconazole (6mg/kg intravenously twice daily on day one, 4mg/kg intravenously twice daily on day two then either 4mg/kg intravenously twice daily or 200mg orally twice daily). Each drug could be administered for up to 84 days.
The primary endpoint, all-cause mortality at day 42, was 18.6% in the isavuconazole group and 20.2% in the voriconazole group, indicating non-inferiority of isavuconazole to voriconazole.
The most common adverse effects (nausea, vomiting, pyrexia and diarrhoea) were reported at similar rates in the two treatment groups. Drug-related adverse effects occurred in 42.4% of patients given isavuconazole and 59.8% of those who received voriconazole. Fewer adverse effects were reported in the isavuconazole groups relating to skin (33.5% vs 43.5%), eyes (15.2% vs 26.6%) and the hepatobiliary tract (8.9% vs 16.2%).