Clinical Research Study: Andexanet Alfa for Enoxaparin Reversal

Andexanet alfa (andexanet) is the only approved reversal agent for patients with acute major bleeding during apixaban or rivaroxaban treatment. Its mechanism suggests it may also reverse the effects of low-molecular-weight heparin.

To evaluate the effects of andexanet in healthy volunteers and in patients with acute major bleeding on enoxaparin.

In the first study, healthy volunteers received enoxaparin 1 mg/kg twice daily for ≥3 doses and were randomized to receive either andexanet or placebo in high- or low-dose regimens, given 3 hours (high dose) or 8 hours (low dose) after the last dose. In the second study (Andexanet Alfa, a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors 4), dosing depended on timing and amount of last enoxaparin dose: high dose if > 40 mg or <8 hours since last dose (or unknown), low dose if ≤ 40 mg or ≥8 hours. The high dose consisted of an 800 mg bolus followed by 960 mg >2 hours, while low dose consisted of a 400 mg bolus followed by 480 mg >2 hours. The primary outcome was change in anti-Xa activity. Hemostatic efficacy was assessed in patients with confirmed bleeding and baseline anti-Xa ≥ 0.25 IU/mL.

In the first study, 24 volunteers received andexanet (12 at a high dose and 12 at a low dose), and 7 received a placebo. Median anti-Xa activity decreased by 83% (0.92-0.17 IU/mL) in the high-dose cohort, and by 73% (0.78-0.22 IU/mL) in the low-dose cohort. In the second study, 22 patients received andexanet; anti-Xa activity decreased by 75% (95% CI, 67%-79%; 0.48-0.14 IU/mL). Good/excellent hemostasis was achieved in 14 of 16 assessable patients (88%).

In enoxaparin-treated subjects, andexanet reduced anti-Xa activity and achieved effective hemostasis in 88% of patients. Results align with findings of patients using apixaban, rivaroxaban, or edoxaban.