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Idorsia announces positive results of the two Japanese registration studies with clazosentan | ||
By: GlobeNewswire - 23 Nov 2020 | Back to overview list |
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Allschwil, Switzerland – November 23, 2020 The program consisted of two double-blind, randomized, placebo-controlled studies assessing the efficacy and safety of clazosentan in reducing vasospasm-related morbidity and all-cause mortality events in adult Japanese patients following aSAH. Patients were randomized to receive continuous infusion of either 10 mg/hr clazosentan or placebo for up to 15 days following the onset of aSAH. The two studies followed the same study design, with one enrolling 221 patients whose aneurysm was secured by surgical clipping and the other enrolling 221 patients whose aneurysm was secured by endovascular coiling. Both studies demonstrated that clazosentan reduced the occurrence of cerebral vasospasm-related morbidity and all-cause mortality within 6 weeks post-aSAH with statistical significance (p<0.01 for both studies). Cerebral vasospasm-related morbidity and all-cause mortality was blindly adjudicated by an independent committee and defined by at least one of the following: All Death / New cerebral infarction due to cerebral vasospasm / Delayed Ischemic Neurologic Deficit (DIND) due to cerebral vasospasm. Clazosentan showed a numerical reduction of all-cause morbidity and mortality in both studies. The effect of clazosentan on this endpoint was significant (p<0.05) in a pre-planned pooled analysis. Further analysis is ongoing including additional pooled analysis of data from both studies. The studies confirmed the well documented safety profile of clazosentan which has now been administered to over 2000 patients around the globe. In these registration studies in Japanese patients post-aSAH there were no unexpected safety findings. Treatment emergent adverse events occurring >5% in 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). Satoshi Tanaka, Dr Med Sci. and President of Idorsia Pharmaceuticals Japan, commented: “I want to start by thanking the investigators and their highly skilled staff for the excellent conduct of the study. I also thank the Idorsia Japan team, many of whom have worked on clazosentan for many years and never doubted the benefit that it could bring to the patients, I’m very proud of the whole team. Most of all I want to thank the patients who have taken part in this study and their families, they can all be very proud of being part of this very important advancement for Japanese patients whose lives are so impacted by this devastating consequence of aSAH. My team will now rapidly analyze the study in full detail with the objective to file the NDA with the PMDA in the first half of 2021 and make the full results available through scientific publication.” Teiji Tominaga, M.D., Ph.D., Professor & Chairman, Department of Neurosurgery, Tohoku University Graduate School of Medicine commented: Jean-Paul Clozel MD and Chief Executive Officer of Idorsia commented: Jean-Paul concluded on a personal note: About the global registration program “REACT” 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. Completion of the study is targeted for the second half of 2022. Notes to the editor Available data in Japanese patients About aneurysmal subarachnoid hemorrhage and cerebral vasospasm The bleeding and the release of a vasoconstrictor (endothelin) by the neighboring vascular endothelium can lead to cerebral vasospasm (constriction of arteries in the brain) usually occurring between four and fourteen days after aSAH. This diminishes blood flow to the brain and about one third of patients consequently experience worsening of their neurological condition. Cerebral vasospasm is one of the leading secondary causes of disability and death in those that experience aSAH. The prevalence of aSAH is estimated to be between 6 and 9 per 100,000 worldwide and is a significant problem in Japan with an incidence around twice as high as in many other countries of the world. Available clinical data with clazosentan This study was followed by two Phase 3 studies, CONSCIOUS-2 and CONSCIOUS-3, to assess the effect of clazosentan on the incidence of cerebral vasospasm-related morbidity and all-cause mortality. The dose of clazosentan (5 mg/h) used in CONSCIOUS-2 did not allow a statistically significant treatment effect to be observed, resulting in the premature termination of CONSCIOUS-3. However, an exploratory analysis of the data collected in CONSCIOUS-3 showed that a higher dose of clazosentan, i.e. 15 mg/h, significantly reduced cerebral vasospasm-related morbidity and all-cause mortality, with a 44% relative risk reduction (p=0.0074). The 15 mg/h dose also significantly reduced the incidence of delayed ischemic neurological deficit with a 54% relative risk reduction (p=0.0038). In addition, clazosentan reduced the need for rescue therapy for vasospasm. Clazosentan did not show any effect of clazosentan on long-term clinical outcome. A Phase 2 study in Japanese and Korean patients showed that 10 mg/hr of clazosentan significantly reduced vasospasm and vasospasm-related morbidity and mortality events. A pilot study evaluating the early effect of clazosentan on reversing established cerebral vasospasm in large proximal cerebral artery segments at three hours post-initiation suggests that clazosentan has the potential to improve large vessel vasospasm upon early administration. In a post-hoc analysis of the effect of clazosentan on reversing established cerebral vasospasm in the entire cerebral vasculature, including smaller distal vessel segments and the cerebellar arteries, a clearly visible improvement in vessel diameter at three and 24 hours could be observed. The above studies have also established an extensive safety profile with over 2,000 patients treated. The side effects of clazosentan are managed based on clear protocol guidelines: hypotension can be mitigated using blood pressure control with vasopressors in the ICU, while lung complications (such as pulmonary edema) can be managed by aiming to maintain euvolemia by avoiding excessive fluid administration. Key literature About Idorsia Headquartered in Switzerland - a biotech-hub of Europe - Idorsia is specialized in the discovery and development of small molecules, to transform the horizon of therapeutic options. Idorsia has a broad portfolio of innovative drugs in the pipeline, an experienced team, a fully-functional research center, and a strong balance sheet – the ideal constellation to bringing R&D efforts to business success. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 800 highly qualified specialists dedicated to realizing our ambitious targets. About Idorsia Pharmaceuticals Japan For further information, please contact The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment |
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