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Clazosentan: First Approval

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Abstract

Clazosentan (PIVLAZ) is a small molecule, endothelin (ET) A receptor-selective antagonist being developed by Idorsia Pharmaceuticals. ETA receptor inhibition by clazosentan decreases ET-related cerebral vasospasm, which may occur after an aneurysmal subarachnoid haemorrhage. Clazosentan has been approved in Japan for use in the prevention of cerebral vasospasm, vasospasm-related cerebral infarction and cerebral ischaemic symptoms after aneurysmal subarachnoid haemorrhage, following the results from the JapicCTI163369 and JapicCTI163368 phase III trials. This article summarises the milestones in the development of clazosentan leading to this first approval in this indication.

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References

  1. Idorsia Pharmaceuticals. Idorsia receives Japanese PMDA approval of PIVLAZ (clazosentan sodium) 150 mg [media release]. http://idorsia.com. 20 Jan 2022.

  2. Idorsia Pharmaceuticals. PIVLAZ (clazosentan) IV infusion liquid 150mg [Japanese prescribing information]. 2022. https://www.pmda.go.jp. Accessed 25 Feb 2022.

  3. Johnson & Johnson. Johnson & Johnson completes acquisition of Actelion [media release]. http://www.janssen.com. 16 Jun 2017.

  4. Axovan. AXOVAN AG announces positive results of phase II trial for clazosentan in vasospasm following subarachnoid hemorrhage [media release]. 12 Aug 2003.

  5. Actelion. Actelion announces 9-month results for 2003 [media release]. http://www.actelion.com. 28 Oct 2003.

  6. Roux S, Breu V, Giller T, et al. Ro 61-1790, a new hydrosoluble endothelin antagonist: general pharmacology and effects on experimental cerebral vasospasm. J Pharmacol Exp Ther. 1997;283(3):1110–8.

    CAS  PubMed  Google Scholar 

  7. Vatter H, Zimmermann M, Tesanovic V, et al. Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction. J Neurosurg. 2005;102(6):1101–7.

    Article  CAS  PubMed  Google Scholar 

  8. Vatter H, Zimmermann M, Tesanovic V, et al. Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: effect on endothelin(B) receptor-mediated relaxation. J Neurosurg. 2005;102(6):1108–14.

    Article  CAS  PubMed  Google Scholar 

  9. Chen G, Tariq A, Ai J, et al. Different effects of clazosentan on consequences of subarachnoid hemorrhage in rats. Brain Res. 2011;1392:132–9.

    Article  CAS  PubMed  Google Scholar 

  10. Juif PE, Dingemanse J, Voors-Pette C, et al. Association between vomiting and QT hysteresis: data from a TQT study with the endothelin A receptor antagonist clazosentan. AAPS J. 2020;22(5):103.

    Article  CAS  PubMed  Google Scholar 

  11. Idorsia Pharmaceuticals. Data on file. 2022.

  12. Idorsia Pharmaceuticals. Idorsia submits NDA for clazosentan to Japanese PMDA [media release]. www.idorsia.com. 1 Mar 2021.

  13. Fujimura M, Joo JY, Kim JS, et al. Preventive effect of clazosentan against cerebral vasospasm after clipping surgery for aneurysmal subarachnoid hemorrhage in Japanese and Korean patients. Cerebrovasc Dis. 2017;44(1–2):59–67.

    Article  CAS  PubMed  Google Scholar 

  14. Macdonald RL, Higashida RT, Keller E, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012;43(6):1463–9.

    Article  CAS  PubMed  Google Scholar 

  15. Macdonald RL, Higashida RT, Keller E, et al. Randomised trial of clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping (CONSCIOUS-2). Acta Neurochir Suppl. 2013;115(7):27–31.

    PubMed  Google Scholar 

  16. Macdonald RL, Kassell NF, Mayer S, et al. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008;39(11):3015–21.

    Article  CAS  PubMed  Google Scholar 

  17. Higashida RT, Bruder N, Gupta R, et al. Reversal of vasospasm with clazosentan after aneurysmal subarachnoid hemorrhage: a pilot study. World Neurosurg. 2019;128:e639–48.

    Article  PubMed  Google Scholar 

  18. Vajkoczy P, Meyer B, Weidauer S, et al. Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebo-controlled, multicenter phase IIa study. J Neurosurg. 2005;103(1):9–17.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Arnold Lee.

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The preparation of this review was not supported by any external funding.

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During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Arnold Lee is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Lee, A. Clazosentan: First Approval. Drugs 82, 697–702 (2022). https://doi.org/10.1007/s40265-022-01708-0

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  • DOI: https://doi.org/10.1007/s40265-022-01708-0

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