TY - JOUR
T1 - Efficacy and safety of isavuconazole against deep-seated mycoses
T2 - A phase 3, randomized, open-label study in Japan
AU - Kohno, Shigeru
AU - Izumikawa, Koichi
AU - Takazono, Takahiro
AU - Miyazaki, Taiga
AU - Yoshida, Minoru
AU - Kamei, Katsuhiko
AU - Ogawa, Kenji
AU - Taniguchi, Shuichi
AU - Akashi, Koichi
AU - Tateda, Kazuhiro
AU - Mukae, Hiroshi
AU - Miyazaki, Yoshitsugu
AU - Okada, Fumito
AU - Kanda, Yoshinobu
AU - Kakeya, Hiroshi
AU - Suzuki, Junko
AU - Kimura, Shun ichi
AU - Kishida, Mitsukazu
AU - Matsuda, Miyuki
AU - Niki, Yoshihito
N1 - Funding Information:
This work was supported by Asahi Kasei Pharma Corporation , Tokyo, Japan. Asahi Kasei Pharma Corporation was involved in the design of the study, the enrollment of patients, the collection, analysis, and interpretation of data, and contributed to the writing of the manuscript.
Funding Information:
Isavuconazole is a triazole antifungal agent with a broad antifungal spectrum [5]. Isavuconazole is available as injectable and oral formulations (with 98% oral bioavailability) [6], both of which have generally linear pharmacokinetics. Since CYP2C9, CYP2C19, CYP2D6, and glucuronosyltransferases, polymorphisms of which affect pharmacokinetics [7,8], are not involved in the metabolism of isavuconazole, no evidence seems to suggest that TDM is required. The injectable formulation lacks β-cyclodextrin and can therefore be administered to patients with renal impairment without dose adjustment [9]. In pivotal phase III studies (SECURE and VITAL studies) [10,11], isavuconazole was shown to be effective against invasive aspergillosis (IA) and mucormycosis, which supported Food and Drug Administration (FDA) and European Medicines Agency (EMA) marketing authorizations. The European Conference on Infections in Leukaemia and European Confederation of Medical Mycology guidelines recommend isavuconazole for use as first-line treatment for IA and primary treatment for mucormycosis [ 12–14]. Furthermore, the VITAL study suggested that isavuconazole is effective in cryptococcosis [15], but the drug does not have an FDA or EMA indication for this.A Data Review Committee (DRC) consisting of infectious disease experts was established for the study. The DRC was independent of the sponsor and investigators. It evaluated diagnostic classifications on enrollment and clinical responses, radiological responses, mycological responses, overall responses, and causes of death on Days 42 and 84 and at EOT. The DRC was blinded to treatment assignment and performed these evaluations for Cohort A, which had a control.This work was supported by Asahi Kasei Pharma Corporation, Tokyo, Japan. Asahi Kasei Pharma Corporation was involved in the design of the study, the enrollment of patients, the collection, analysis, and interpretation of data, and contributed to the writing of the manuscript.
Publisher Copyright:
© 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
PY - 2023/2
Y1 - 2023/2
N2 - Objectives: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses. Patients and methods: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT). Results: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole. Conclusions: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated.
AB - Objectives: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses. Patients and methods: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT). Results: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole. Conclusions: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated.
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U2 - 10.1016/j.jiac.2022.10.010
DO - 10.1016/j.jiac.2022.10.010
M3 - Article
C2 - 36307059
AN - SCOPUS:85141321562
SN - 1341-321X
VL - 29
SP - 163
EP - 170
JO - Journal of Infection and Chemotherapy
JF - Journal of Infection and Chemotherapy
IS - 2
ER -
