Earlier this month, the FDA approved a biologic agent known as Andexanet alfa (Andexxa), manufactured by Portola, indicated for the reversal of anticoagulation from factor Xa inhibitors, specifically apixaban (Eliquis) and rivaroxaban (Xarelto). This represents a major advancement in the treatment of hospitalized patients facing life-threatening bleeding.
Patients can be on factor Xa inhibitors for a variety of reasons; venous thromboembolism (VTE) prevention and treatment, stroke prevention in atrial fibrillation patients, and overall reduction in risk of recurrence of VTE. Factor Xa inhibitors work by directly inhibiting factor Xa, a necessary enzyme of the coagulation cascade, resulting in platelet and fibrin inhibition. This prevents the formation of blood clots in the body and is especially crucial in patients who have already experienced VTE. Because of their ease of use, little monitoring required, and convenient dosing schedules, factor Xa inhibitors are usually drugs for patients leaving the hospital but who still need to be anticoagulated long-term. Factor Xa inhibitors like apixaban and rivaroxaban have many advantages when compared to agents such as warfarin and enoxaparin in preventing and treating thromboembolic condition. As with any medications, there are pros and cons. In this case, over-anticoagulation can lead to an increased risk of bleeding and potentially in a fatal way.
Currently, alternatives to factor Xa inhibitors all have reversal agents available in the hospital but provide suboptimal reversal. This new FDA approval provides safety for those taking factor Xa inhibitors and allows for safety mechanisms in cases of excess bleeding due to them. The value of Andexanet alfa cannot be understated from a patient’s and healthcare provider’s point of view. According to Portola’s CEO, there were more than 117,000 hospital admissions for uncontrolled bleeding for which Andexxa could have been used. Not only does drug approval provide prescribers greater confidence in the prescribing of Xarelto and Eliquis, it grants patients greater confidence in their own safety while taking the medications and overall provides a higher value of health care. Andexxa will be very limited over the next year but expect it to make a great impact when it’s second generation of manufacturing kicks in.
- Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. New England Journal of Medicine 2016;375(12):1131–41.
- Package insert for Andexxa. https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM606687.pdf