Asundexian

Asundexian
Legal status
Legal status
  • Investigational
Identifiers
  • 4-[[(2S)-2-[4-[5-Chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC26H21ClF4N6O4
Molar mass592.94 g·mol−1
3D model (JSmol)
  • CC[C@@H](C(=O)NC1=CC(=C(C=C1)C(=O)N)F)N2C=C(C(=CC2=O)C3=C(C=CC(=C3)Cl)N4C=C(N=N4)C(F)(F)F)OC
  • InChI=1S/C26H21ClF4N6O4/c1-3-19(25(40)33-14-5-6-15(24(32)39)18(28)9-14)36-11-21(41-2)17(10-23(36)38)16-8-13(27)4-7-20(16)37-12-22(34-35-37)26(29,30)31/h4-12,19H,3H2,1-2H3,(H2,32,39)(H,33,40)/t19-/m0/s1
  • Key:XYWIPYBIIRTJMM-IBGZPJMESA-N

Asundexian[1] is a Factor XIa inhibitor developed by Bayer to prevent stroke.[2]

Clinical trial(s)

Asundexian efficacy and safety in patients have been evaluated in two clinical trial programs: phase IIb PACIFIC and phase III OCEANIC.[3] In the phase IIb PACIFIC clinical trial programs, asundexian consistently showed no difference in bleeding rate compared with placebo[4][5] and reduced the risk of bleeding compared with apixaban.[6] All three trials in the programs were not powered to show efficacy of asundexian.[3] However, a phase III trial, OCEANIC-AF, demonstrated a hazard ratio of 3.8 for stroke or systemic embolism with asundexian vs apixaban, so it was stopped due to a "lack of efficacy." The remaining active study OCEANIC-STROKE was recommended to continue as planned. Bayer is reevaluating the design of the OCEANIC-AFINA based on the findings of the OCEANIC trial.[7]

In February 2026, the OCEANIC-STROKE trial was completed. This was a multicentre, randomised, double-blind, placebo-controlled study involving 12,000 people worldwide who had suffered a non-cardioembolic ischaemic stroke or a transient ischaemic attack. The trial revealed a 26% reduction in the rate of recurrence without major bleeding, a typical complication of antithrombotic drugs.[8][9][10]

References

  1. ↑ Roehrig, Susanne; Ackerstaff, Jens; Jiménez Núñez, Eloísa; Teller, Henrik; Ellerbrock, Pascal; Meier, Katharina; Heitmeier, Stefan; Tersteegen, Adrian; Stampfuss, Jan; Lang, Dieter; Schlemmer, Karl-Heinz; Schaefer, Martina; Gericke, Kersten M.; Kinzel, Tom; Meibom, Daniel (2023-09-05). "Design and Preclinical Characterization Program toward Asundexian (BAY 2433334), an Oral Factor XIa Inhibitor for the Prevention and Treatment of Thromboembolic Disorders". Journal of Medicinal Chemistry. 66 (17): 12203–12224. doi:10.1021/acs.jmedchem.3c00795. ISSN 0022-2623. PMC 10510402. PMID 37669040.
  2. ↑ Heitmeier, Stefan; Visser, Mayken; Tersteegen, Adrian; Dietze-Torres, Julia; Glunz, Julia; Gerdes, Christoph; Laux, Volker; Stampfuss, Jan; Roehrig, Susanne (June 2022). "Pharmacological profile of asundexian, a novel, orally bioavailable inhibitor of factor XIa". Journal of Thrombosis and Haemostasis. 20 (6): 1400–1411. doi:10.1111/jth.15700. PMC 9313898. PMID 35289054.
  3. 1 2 "Bayer initiates landmark Phase III study program to investigate oral FXIa inhibitor asundexian". Bayer (Press release). 2022-08-28. Retrieved 2023-12-27.
  4. ↑ "AntiCoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334 – Non-cardioembolic Stroke". American College of Cardiology. Retrieved 2023-12-26.
  5. ↑ Rao, Sunil V.; Kirsch, Bodo; Bhatt, Deepak L.; Budaj, Andrzej; Coppolecchia, Rosa; Eikelboom, John; James, Stefan K.; Jones, W. Schuyler; Merkely, Bela; Keller, Lars; Hermanides, Renicus S.; Campo, Gianluca; Ferreiro, José Luis; Shibasaki, Taro; Mundl, Hardi (2022-10-18). "A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction". Circulation. 146 (16): 1196–1206. doi:10.1161/CIRCULATIONAHA.122.061612. hdl:11392/2520330. ISSN 0009-7322. PMID 36030390.
  6. ↑ "The Next Wave of Anticoagulation: Results of PACIFIC-AF and the Future Role of Factor XIa Inhibition in Atrial Fibrillation". American College of Cardiology. Retrieved 2023-12-26.
  7. ↑ "OCEANIC-AF study stopped early due to lack of efficacy". Bayer (Press release). 2023-11-19. Retrieved 2023-12-27.
  8. ↑ doi:10.1056/NEJMoa2407105
  9. ↑ "Ictus ischemico, i risultati della ricerca su un nuovo farmaco sperimentale: recidive ridotte del 26%". Ospedale Maggiore di Bologna (in Italian).{{cite web}}: CS1 maint: deprecated archival service (link)
  10. ↑ "Bayer's asundexian demonstrated a substantial 26% reduction in stroke after a non-cardioembolic ischemic stroke or high-risk transient ischemic attack, with no increase in ISTH major bleeding versus placebo". Bayer.{{cite web}}: CS1 maint: deprecated archival service (link)
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