Idorsia submits NDA for clazosentan to Japanese PMDA

Idorsia submits NDA for clazosentan to Japanese PMDA

Allschwil, Switzerland – March 1, 2021

Idorsia Ltd (SIX: IDIA) today announced the submission of a New Drug Application (NDA) to the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for clazosentan, a fast-acting, selective endothelin A (ET_A) receptor antagonist, for the prevention of cerebral vasospasm, vasospasm-related cerebral infarction and cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage (aSAH).

The application is supported by replicated results from the Japanese registration program which 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 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.

Satoshi Tanaka, Dr Med Sci. and President of Idorsia Pharmaceuticals Japan, commented:
“The development of clazosentan has taken many years to bring us to the filing of an NDA and we were very fortunate to not be held back by the COVID-19 pandemic in Japan. The team has worked rapidly to analyze the data and prepare the dossier for the PMDA so that we can bring clazosentan to the patients as soon as possible. We will now work together with the authorities through the regulatory process, and in parallel, prepare the scientific publication and the commercial launch which we hope to see in the first half of 2022.”

Both studies showed 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). The composite endpoint was defined by at least one of the following: All death / New cerebral infarction due to cerebral vasospasm / Delayed ischemic neurologic deficit due to cerebral vasospasm and adjudicated blindly by an independent committee. The effect of clazosentan on all-cause morbidity and mortality was also significant (p<0.05) in a pre-planned analysis of the pooled studies whereas a numerical trend was observed in each study on this endpoint.

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).