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XARELTO®

(rivaroxaban)

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XARELTO® (rivaroxaban)

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SPECIFIC RESPONSE

XARELTO - Reversal Agents in Human Studies - Andexanet alfaa (PRT064445) - ANNEXA-4

Last updated : 05/16/2024

ANNEXA-4 is a multicenter, prospective, open-label, single-group study that assessed the efficacy and safety of andexanet in 352 patients with acute major bleeding within 18 hours after the administration of a factor Xa inhibitor.1

Study Design1

Study Population1

  • The efficacy population (n=254) included those who met the criteria for bleeding severity and had baseline anti–factor Xa activity of ≥75 ng/mL or ≥0.25 IU/mL for those receiving enoxaparin.
  • The safety population (n=352) included all patients who received andexanet.

Baseline Characteristics1

Percent Change in Anti–factor Xa Activity at the End of Bolus Administration (Efficacy Population)1

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XARELTO Patients
(n=100)

Apixaban Patients
(n=134)

Enoxaparin Patients
(n=16)

Median anti–factor Xa activity reduction

Baseline

211.8 ng/mL

149.7 ng/mL

0.48 IU/mL

End of bolus administration

14.2 ng/mL

11.1 ng/mL

0.15 IU/mL

Percent reduction (95% CI)

92 (88-94)

92 (91-93)

75 (66-79)

Percent reduction in median anti–factor Xa activity from baseline at different timepoints after andexanet infusion , %

4 hours

42

32

–

8 hours

48

34

–

12 hours

62

38

–

NOTE: Efficacy analysis is not shown for the 4 patients who received edoxaban.

Hemostatic Efficacy 12 Hours After Andexanet Infusion (Efficacy Population)1

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aAndexxa® (coagulation factor Xa [recombinant], inactivated-zhzo) is a product of AstraZeneca. Please refer to the Andexxa Prescribing Information for complete product information or call AstraZeneca at 1-800-236-9933.
bAcute major bleeding was defined as bleeding that had ≥1 of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of ≥2 g/dL (or a hemoglobin level of ≤8 g/dL if no baseline hemoglobin level was available); or bleeding in a critical area or organ.
cOf the 249 patients who could be evaluated for hemostatic efficacy, 204 (82%) had excellent (n=171) or good (n=33) hemostatic efficacy at 12 hours.

CI, confidence interval; GI, gastrointestinal; ICH, intracranial hemorrhage; PCC, prothrombin complex concentrate; rFVIIa, recombinant factor VIIa; VKA, vitamin K antagonist.

Deaths: In the safety population, death occurred in 14% (n=49) of patients during the 30-day follow-up period.1

Thrombotic events occurred in 10% (n=34) of patients during the 30-day follow-up period.1

  • There were 11 thrombotic events within 5 days after andexanet therapy, 11 thrombotic events between 6 and 14 days, and 12 thrombotic events between 15 and 30 days.

Neutralizing Antibodies: Antibodies to factor X or Xa did not develop in any patients after andexanet treatment, and no neutralizing antibodies to andexanet developed.1

Anticoagulant therapy was immediately discontinued at the time of enrollment.1

  • During the 30 days after andexanet treatment, 62% (n=220) received at least 1 dose of parenteral or oral anticoagulant therapy, of whom 2% (n=8) experienced a thrombotic event.
  • Twenty-eight percent were restarted on oral anticoagulant therapy during follow-up, in which no thrombotic events occurred.

There was no significant relationship between reduction in anti–factor Xa activity and hemostatic efficacy overall, but it was modestly predictive in patients with ICH.1

aAndexxa® (coagulation factor Xa [recombinant], inactivated-zhzo) is a product of AstraZeneca. Please refer to the Andexxa Prescribing Information for complete product information or call AstraZeneca at 1-800-236-9933.
bAcute major bleeding was defined as bleeding that had ≥1 of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of ≥2 g/dL (or a hemoglobin level of ≤8 g/dL if no baseline hemoglobin level was available); or bleeding in a critical area or organ.

GI, gastrointestinal; ICH, intracranial hemorrhage; PCC, prothrombin complex concentrate; rFVIIa, recombinant factor VIIa; VKA, vitamin K antagonist.

aAndexxa® (coagulation factor Xa [recombinant], inactivated-zhzo) is a product of AstraZeneca. Please refer to the Andexxa Prescribing Information for complete product information or call AstraZeneca at 1-800-236-9933.
bAcute major bleeding was defined as bleeding that had ≥1 of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of ≥2 g/dL (or a hemoglobin level of ≤8 g/dL if no baseline hemoglobin level was available); or bleeding in a critical area or organ.

GI, gastrointestinal; ICH, intracranial hemorrhage; PCC, prothrombin complex concentrate; VKA, vitamin K antagonist.

Reference

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1. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380(14):1326-1335.