Asundexian
{{Short description|Chemical compound}}
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| legal_status = Investigational
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| CAS_number = 2064121-65-7
| PubChem = 135206011
| UNII = LA585UM8DE
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| KEGG = D12838
| ChemSpiderID = 115009501
| StdInChI=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
| StdInChIKey = XYWIPYBIIRTJMM-IBGZPJMESA-N
| SMILES = 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
| IUPAC_name = 4-
| C = 26 | H = 21 | Cl = 1 | F = 4 | N = 6 | O = 4
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Asundexian is a Factor XIa inhibitor developed by Bayer to prevent stroke.{{cite journal |last1=Heitmeier |first1=Stefan |last2=Visser |first2=Mayken |last3=Tersteegen |first3=Adrian |last4=Dietze-Torres |first4=Julia |last5=Glunz |first5=Julia |last6=Gerdes |first6=Christoph |last7=Laux |first7=Volker |last8=Stampfuss |first8=Jan |last9=Roehrig |first9=Susanne |title=Pharmacological profile of asundexian, a novel, orally bioavailable inhibitor of factor XIa |journal=Journal of Thrombosis and Haemostasis |date=June 2022 |volume=20 |issue=6 |pages=1400–1411 |doi=10.1111/jth.15700|pmid=35289054 |pmc=9313898 }}
Clinical trial(s)
Asundexian efficacy and safety in patients have been evaluated in two clinical trial programs: phase IIb PACIFIC and phase III OCEANIC.{{cite web |date=2022-08-28 |title=Bayer initiates landmark Phase III study program to investigate oral FXIa inhibitor asundexian |url=https://www.bayer.com/media/en-us/bayer-initiates-landmark-phase-iii-study-program-to-investigate-oral-fxia-inhibitor-asundexian/ |access-date=2023-12-27 |website=Bayer |type=Press release}} In the phase IIb PACIFIC clinical trial programs, asundexian consistently showed no difference in bleeding rate compared with placebo{{cite web |title=AntiCoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334 – Non-cardioembolic Stroke |url=https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2022/08/27/04/10/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fClinical-Trials%2f2022%2f08%2f27%2f04%2f10%2fPACIFIC-STROKE |access-date=2023-12-26 |website=American College of Cardiology}}{{cite journal |last1=Rao |first1=Sunil V. |last2=Kirsch |first2=Bodo |last3=Bhatt |first3=Deepak L. |last4=Budaj |first4=Andrzej |last5=Coppolecchia |first5=Rosa |last6=Eikelboom |first6=John |last7=James |first7=Stefan K. |last8=Jones |first8=W. Schuyler |last9=Merkely |first9=Bela |last10=Keller |first10=Lars |last11=Hermanides |first11=Renicus S. |last12=Campo |first12=Gianluca |last13=Ferreiro |first13=José Luis |last14=Shibasaki |first14=Taro |last15=Mundl |first15=Hardi |date=2022-10-18 |title=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 |journal=Circulation |language=en |volume=146 |issue=16 |pages=1196–1206 |doi=10.1161/CIRCULATIONAHA.122.061612 |issn=0009-7322|doi-access=free |pmid=36030390 |hdl=11392/2520330 |hdl-access=free }} and reduced the risk of bleeding compared with apixaban.{{cite web |title=The Next Wave of Anticoagulation: Results of PACIFIC-AF and the Future Role of Factor XIa Inhibition in Atrial Fibrillation |url=https://www.acc.org/Latest-in-Cardiology/Articles/2022/06/17/11/54/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2022%2f06%2f17%2f11%2f54%2fThe-Next-Wave-of-Anticoagulation |access-date=2023-12-26 |website=American College of Cardiology}} All three trials in the programs were not powered to show efficacy of asundexian. 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.{{cite web |date=2023-11-19 |title=OCEANIC-AF study stopped early due to lack of efficacy |url=https://www.bayer.com/media/en-us/oceanic-af-study-stopped-early-due-to-lack-of-efficacy/ |access-date=2023-12-27 |website=Bayer |type=Press release}}