Milvexian phase 2 data supports safety and efficacy for VTE prevention after total knee replacement

Milvexian, a novel factor XIa inhibitor, was associated with a reduced risk of post-operative venous thromboembolism (VTE) after total knee replacement surgery in the phase 2 AXIOMATIC-TKR trial. Moreover, the associated risk of bleeding was low for this treatment. The promising results of this trial confirm the emerging role of factor XI inhibition in anticoagulation.

Milvexian is an oral, small molecule, factor XIa inhibitor. “Factor XI is an exciting target for anticoagulant therapies since there is mounting evidence that factor XI is important for thrombosis but mostly dispensable for haemostasis,” said Prof. Jeffrey Weitz (McMaster University, Canada) [1]. “Therefore, factor-XI inhibitors are potentially safer than downstream inhibitors, such as agents targeting factor Xa.”

The prospective, randomised, phase 2 AXIOMATIC-TKR trial (NCT03891524) aimed to assess the efficacy and safety of milvexian regarding postoperative VTE [2]. The primary efficacy outcome was VTE (i.e. asymptomatic deep vein thrombosis, symptomatic VTE, or death). The principal safety outcome was any bleeding. In total, 1,242 participants were randomised over 7 milvexian arms (i.e. 25 mg, 50 mg, 200 mg once daily, or 25 mg, 50 mg, 100 mg, 200 mg twice daily) or enoxaparin (40 mg once daily).

After 14 days of therapy, the combined milvexian twice-daily doses were associated with significantly fewer VTE events (12.2%) compared with the prespecified benchmark of 30% (P<0.0001). Moreover, a significant dose-response was observed with the twice-daily doses (P=0.0004). The rates of VTE events were significantly lower in the 200 mg twice daily group (8%), 100 mg twice daily group (9%), 50 mg twice daily group (11%), and the 200 mg once daily group (7%) compared with enoxaparin receivers (21%).

Similar rates of any bleedings occurred in patients receiving milvexian and patients receiving enoxaparin (both 4%). Clinically relevant bleeding was reported in 1% of the milvexian receivers. No major bleeding was observed in the milvexian arms. Any adverse events were equally divided across enoxaparin (38%) and milvexian (39%) receivers.

In conclusion, the results of AXIOMATIC-TXR supported the efficacy of the oral factor XIa inhibitor milvexian and showed a favourable bleeding profile.

1. 
   
   1. Weitz JI, et al. Milvexianfor prevention of venous thromboembolism after elective knee arthroplasty: The AXIOMATIC-TKR Study. LBS07, AHA Scientific Sessions 2021, 13–15 November.
   2. Weitz JI, et al. N Engl J Med 2021;385:2161–2172.

 

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Posted on 14 January 202229 February 2024