Efficacy and safety of isavuconazole against deep-seated mycoses: A phase 3, randomized, open-label study in Japan.

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.

24-Month Open-Label Teriparatide Once-Weekly Efficacy Research Trial Examining Bone Mineral Density in Subjects with Primary Osteoporosis and High Fracture Risk.

INTRODUCTION: To clarify the additional efficacy and safety benefits of 24 months' treatment with the once-weekly formulation of teriparatide, which is currently used for 72 weeks. METHODS: This was a multicenter, open-label, single-arm study conducted in Japan. Subjects who were 65 years or older with prevalent vertebral fractures received once-weekly subcutaneous injection of 56.5 µg teriparatide for 24 months. The main outcome measure was percentage change from baseline in lumbar (L2-L4) BMD measured by dual-energy X-ray absorptiometry. RESULTS: A total of 189 subjects received at least one dose of the once-weekly formulation of teriparatide. Lumbar, femoral neck, and total hip BMD increased significantly compared with baseline at Weeks 24, 48, 72, and 104. In addition, significant increases in lumbar (+1.5%) and femoral neck (+0.8%) BMD were noted at Week 104 compared with Week 72. Significant increases from baseline in BMD for radius 1/10 were noted at Weeks 24 and 104. No substantial increases were noted in the cumulative incidences of new vertebral fracture and other types of fracture after Week 72. The safety profile seen in the first 72 weeks remained unchanged until 104 weeks. CONCLUSION: The once-weekly formulation of teriparatide is effective and safe for the treatment of osteoporosis over 24 months. The limitation of this study is that this was an open-label, single-arm study. FUNDING: Asahi Kasei Pharma Corporation. CLINICAL TRIAL REGISTRATION: JapicCTI-132276.