Idorsia submits NDA for clazosentan to Japanese PMDA - Seite 2
The studies confirmed the well-documented safety profile of clazosentan which has now been administered to approximately 2000 patients around the world. In these registration studies in Japanese patients post-aSAH there were no unexpected safety findings. Treatment-emergent adverse events occurring in >5% of the clazosentan group (with a difference of >2% compared to placebo) were vomiting and signs of hemodilution or fluid retention (i.e., hyponatremia, hypoalbuminemia, anemia, pleural effusion, brain and pulmonary edema).
Notes to the editor
Available data in Japanese patients
A Phase 2 study in Japanese and Korean patients showed that 10 mg/hr of clazosentan administered by continuous intravenous infusion significantly reduced vasospasm and vasospasm-related morbidity and mortality events. The results are published in Cerebrovascular Diseases (Fujimura M, et al. Cerebrovasc Dis 2017;44:59–67). On that basis, a registration program was initiated with clazosentan in Japan in May 2016.
About the global registration program “REACT”
In February 2019, Idorsia initiated REACT, a prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group, Phase 3 study to investigate the efficacy and safety of clazosentan for the prevention of clinical deterioration due to vasospasm-related delayed cerebral ischemia in adult patients following aSAH. The Phase 3 study builds upon the learnings from the previous clazosentan studies to identify patients at high risk of vasospasm and delayed cerebral ischemia, the optimal dose, the best measure to demonstrate efficacy and an optimized patient management guideline to ensure patient safety.
Approximately 400 patients – treated either with microsurgical clipping or endovascular coiling – are being enrolled at approximately 95 sites across 15 countries. Patients are randomized to receive continuous infusion of either clazosentan (15 mg/hr) or placebo prophylactically, on top of local standard of care, for a period of up to 14 days. REACT is enrolling aSAH patients identified as being at high risk of developing vasospasm and subsequent delayed cerebral ischemia because of high-volume hemorrhage, as assessed by CT scan on hospital admission. Patients experiencing asymptomatic cerebral vasospasm, as measured by angiography, within 14 days of aSAH may also be included. Results of the study are targeted for the second half of 2022.