F11a and FX12a Inhibitors – the Next Wave of Novel Anticoagulants?​

Anticoagulation treatment has been revolutionised in the past few decades with the development of drugs that increasingly target individual components of the coagulation cascade. Yet the quest to find improved solutions that prevent thrombosis without causing too much bleeding, particularly in patients at higher risk, continues.


During the ‘Back to the Future’ session, Sarah Lessire (Université Catholique de Louvain, Belgium) highlighted some of the newest players in the game, the factor 11 (FXI) and factor 12 (FXII) inhibitors. These drugs target the contact pathway of coagulation, which has previously been thought to have a limited role in preventing thrombosis.1


Up until a few years ago the direct-acting oral anticoagulants (DOACs) were the newest drugs available. Those were much needed as they improved upon the pharmacokinetics of older drugs such as the lower molecular weight heparins, unfractionated heparin and warfarin, meaning that they could be taken orally. DOACs also took away the need for regular coagulation monitoring and, perhaps more importantly, promised a reduced risk for bleeding complications.


“We had a couple of issues with the DOACs because some subgroups of patients were excluded from phase III clinical trials,” says Lessire. For example, older patients, those with severe renal insufficiency, and other comorbidities involving higher bleeding tendency.


“We now have these drugs on the market, but we still are currently facing major bleeding, and clinically relevant non-major bleeding in patients at higher risk of bleeding,” she adds.


So, there is still room for improvement which is where targeting FXI and FXII has gained interest. Theoretically these new drugs should be associated with few bleeding complications.


There are several FXIa and FXIIa inhibitors in clinical development, most are in phase II trials, but some are in phase III. These are both for oral or parenteral administration, and currently need to be given daily, weekly, or even monthly.


“We still have to see in which patients they will be the most effective,” says Lessire. Their safety and efficacy will need to be compared with current anticoagulants in several specific indications. They also need to be tested in combination with other approaches, such as antiplatelet therapy.  


Although still investigational and a long way from becoming routinely used, FXI and FXII inhibitors are already in hospitals participating in the clinical trials.


“These drugs are coming now,” Lessire points out, patients may be taking them when they come into the hospital for an emergency and what should be done if they experience bleeding? “We need to know which drug it is, we need to know the monitoring, and also the management,” she says. So, hospitals and their clinicians need to be prepared and have a plan for encountering these agents, even if they are not yet on the market. The results of phase II trials seem to be reassuring at least concerning their bleeding risk, Lessire says.




  1. Cohen O, Ageno W. Coming soon to a pharmacy near you? FXI and FXII inhibitors to prevent or treat thromboembolism. Hematology Am Soc Hematol Educ Program. 2022;2022(1):495–505.

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