Aprocitentan

Aprocitentan
Clinical data
Trade namesTryvio
Other namesACT-132577
AHFS/Drugs.comMonograph
Routes of
administration		By mouth
Drug classAntihypertensive
ATC code
Legal status
Legal status
Identifiers
  • 5-(4-Bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-(sulfamoylamino)pyrimidine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC16H14Br2N6O4S
Molar mass546.19 g·mol−1
3D model (JSmol)
  • C1=CC(=CC=C1C2=C(N=CN=C2OCCOC3=NC=C(C=N3)Br)NS(=O)(=O)N)Br
  • InChI=1S/C16H14Br2N6O4S/c17-11-3-1-10(2-4-11)13-14(24-29(19,25)26)22-9-23-15(13)27-5-6-28-16-20-7-12(18)8-21-16/h1-4,7-9H,5-6H2,(H2,19,25,26)(H,22,23,24)
  • Key:DKULOVKANLVDEA-UHFFFAOYSA-N

Aprocitentan, sold under the brand name Tryvio, is a medication used to treat hypertension (high blood pressure).[1] It is developed by Idorsia.[4] It is taken by mouth.[1]

Aprocitentan is a receptor antagonist that targets both endothelin A and endothelin B receptors.[5][6]

Aprocitentan was approved for medical use in the United States in March 2024.[1][4][7] It is the first endothelin receptor antagonist to be approved by the US Food and Drug Administration (FDA) to treat systemic hypertension.[4]

Medical uses

Aprocitentan is indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adults who are not adequately controlled on other medications.[1]

Adverse effects

Aprocitentan may cause hepatotoxicity (liver damage), edema (fluid retention), anemia (reduced hemoglobin), and decreased sperm count.[1]

Contraindications

Data from animal reproductive toxicity studies with other endothelin-receptor agonists indicate that use is contraindicated in pregnant women.[1]

Mechanism of action

Aprocitentan is an endothelin receptor antagonist that inhibits the protein endothelin-1 from binding to endothelin A and endothelin B receptors.[1][6] Endothelin-1 mediates various adverse effects via its receptors, such as inflammation, cell proliferation, fibrosis, and vasoconstriction.[1]

Society and culture

Economics

Aprocitentan is developed by Idorsia, which sold it to Janssen and purchased the rights back in 2023, for US$343 million.[8]

Aprocitentan was approved for medical use in the United States in March 2024.[1]

In April 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Jeraygo, intended for the treatment of resistant hypertension in adults.[2][9] The applicant for this medicinal product is Idorsia Pharmaceuticals Deutschland GmbH.[2] Aprocitentan was approved for medical use in the European Union in June 2024.[2][3]

References

  1. ^ a b c d e f g h i j "Tryvio- aprocitentan tablet, film coated". DailyMed. 29 March 2024. Archived from the original on 25 April 2024. Retrieved 25 April 2024.
  2. ^ a b c d "Jeraygo EPAR". European Medicines Agency. 25 April 2024. Archived from the original on 13 June 2024. Retrieved 13 June 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ^ a b "Jeraygo PI". Union Register of medicinal products. 28 June 2024. Retrieved 5 July 2024.
  4. ^ a b c "US FDA approves Idorsia's once-daily Tryvio (aprocitentan) - the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with other antihypertensives" (Press release). Idorsia. 20 March 2024. Archived from the original on 28 April 2024. Retrieved 28 April 2024 – via PR Newswire.
  5. ^ Ojha, Utkarsh; Ruddaraju, Sanjay; Sabapathy, Navukkarasu; Ravindran, Varun; Worapongsatitaya, Pitchaya; Haq, Jeesanul; et al. (2022). "Current and Emerging Classes of Pharmacological Agents for the Management of Hypertension". American Journal of Cardiovascular Drugs. 22 (3): 271–285. doi:10.1007/s40256-021-00510-9. PMC 8651502. PMID 34878631.
  6. ^ a b Xu, Jingjing; Jiang, Xiaohua; Xu, Suowen (November 2023). "Aprocitentan, a dual endothelin-1 (ET-1) antagonist for treating resistant hypertension: Mechanism of action and therapeutic potential". Drug Discovery Today. 28 (11): 103788. doi:10.1016/j.drudis.2023.103788. PMID 37742911.
  7. ^ "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 30 April 2024. Retrieved 30 April 2024.
  8. ^ Deswal, Phalguni (6 September 2023). "Idorsia reacquires aprocitentan rights from Janssen for $343m". Pharmaceutical Technology. Archived from the original on 8 November 2023. Retrieved 8 November 2023.
  9. ^ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2024". European Medicines Agency (Press release). 26 April 2024. Archived from the original on 5 July 2024. Retrieved 13 June 2024.

Further reading

  • Mahfooz K, Najeed S, Tun HN, Khamosh M, Grewal D, Hussain A, et al. (July 2023). "New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension: A Systematic Review and Meta-Analysis". Current Problems in Cardiology. 48 (7): 101686. doi:10.1016/j.cpcardiol.2023.101686. PMID 36893968.